Tag Archives: ovarian cancer

2011 Pharmaceutical Research & Manufacturers of America Report Lists 58 Drugs in Development For Ovarian Cancer

Posted on by

Currently, 851 medicines are in development for diseases that exclusively or disproportionately affect women, according to a report unveiled today by the Pharmaceutical Research and Manufacturers of America (PhRMA).

Currently, 851 medicines are in development for diseases that exclusively or disproportionately affect women, according to a report unveiled today by the Pharmaceutical Research and Manufacturers of America (PhRMA).  The medicines in the pipeline for women (either in human clinical trials or awaiting review by the Food and Drug Administration) include:

• 139 for cancers affecting women, including 91 for breast cancer, 49 for ovarian cancer,[1] and 9 for cervical cancer.

• 114 for arthritis/musculoskeletal disorders. Approximately 46 million Americans have some type of arthritis or related condition, and 60 percent of them are female.

• 64 for obstetric/gynecologic conditions.

• 110 for autoimmune diseases, which strike women three times more than men.

• 72 for depression and anxiety. Almost twice as many women as men suffer from these disorders.

• 83 for Alzheimer’s disease. Two-thirds (3.4 million) of the 5.4 million Americans living with Alzheimer’s today are women.

The Drug Discovery Process

Ovarian cancer affected an estimated 21,880 U.S. women in 2010 and caused an estimated 13,850 deaths.  The PhRMA report highlighted a potential first-in-class ovarian cancer drug (volasertib/BI 6727) in development which works by selectively inhibiting the polo-like kinase-1 (PLK-1), an enzyme crucial for cell division. PLK-1 is expressed in proliferating cells and most tumors. Inhibiting its activity disrupts cell division, which induces cell death and reduces cancer growth.

The ovarian cancer drugs listed in the PhRMA report are listed below by name (brand name, if available, and generic name), manufacturer, and phase of clinical testing. The ovarian cancer drugs listed in the “Cancer” section of the PhRMA report are set forth below:[2]

A6, Angstrom Pharmaceuticals, Phase II.

Abagovomab (anti-idiotype ovarian cancer vaccine)(Orphan Drug), Menarini, Phase I/II.

Abraxane®/albumin-bound paclitaxel, Celgene, Phase II.

ABT-888/veliparib, Abbott Laboratories, Phase II.

AE-37, Antigen Express, Phase I.

Afinitor®/everolimus, Novartis Pharmaceuticals, Phase I/II.

AMG 386, Amgen, Phase III.

AMG 479, Amgen, Phase II.

Avastin®, bevacizumab, Genentech, Phase III.

BC-819, BioCancell Therapeutics, Phase I/II.

Catumaxomab, Fresenius Biotech, Phase II.

CVac™/MUC-2 cancer vaccine, Prima BioMed, Phase II.

DCVax®-L/ovarian cancer vaccine, Northwest Biotherapeutics, Phase I.

DPX-0907, Immunovaccine, Phase I.

EC-145, Endocyte, Phase II.

EGEN-001 (Orphan Drug), EGEN, Phase I/II.

ENMD-2076, EntreMed, Phase II.

Estybon™/ON-01910.Na, Onconova Therapeutics, Phase II.

Evizon™/squalamine, OHR Pharmaceuticals, Phase II.

farletuzumab/MORAb-003, Eisai, Phase III.

iboctadekin, GlaxoSmithKline, Phase I.

IMT-1012/immunotherapeutic vaccine, Immunotope, Phase I.

iniparib/BSI-201, BiPar Sciences/sanofi-aventis, Phase II.

Karenitecin®/cositecan, BioNumerik Pharmaceuticals, Phase III.

KHK-2866, Kyowa Hakko Kirin Pharma, Phase I.

lenvatinib/E7080, Eisai, Phase II.

MK-2206, Merck, Phase I.

Nexavar®/sorafenib, Bayer HealthCare Pharmaceuticals/Onyx Pharmaceuticals, Phase II.

NKTR-102, Nektar Therapeutics, Phase II.

NOV-002, Novelos Therapeutics, Phase II.

OGX-427, Oncogenex Pharmaceuticals, Phase I.

olaparib/AZD2281, AstraZeneca, Phase II.

Opaxio™/paclitaxel poliglumex, Cell Therapeutics/Novartis Pharmaceuticals, Phase III.

Optisome™/topetecan liposomal, Talon Therapeutics, Phase I.

Oregovomab, Quest Pharmatech, Phase I/II.

OSI-906/linsitinib, OSI Pharmaceuticals, Phase II.

OVax®/ovarian cancer vaccine (Orphan Drug), AVAX Technologies, Phase I/II.

Perifosine/KRX-0401, AEterna Zentaris/Keryx Biopharmaceuticals, Phase I.

PF-01367338, Pfizer, Phase II.

Phenoxodiol (next generation drug will be NV-143), Marshall Edwards, Phase III.

Picoplatin intravenous, Poniard Pharmaceuticals, Phase II.

Quinamed®/amonafide, ChemGenex Pharmaceuticals, Phase II.

Ramucirumab/IMC-1121-B, Eli Lilly/ImClone, Phase I.

Ridaforolimus, Merck/Ariad Pharmaceuticals, Phase I.

Sagopilone, Bayer HealthCare Pharmaceuticals, Phase II.

SAR256212/MM-121, Merrimack Pharmaceuticals/sanofi-aventis, Phase I.

SG2000, Spirogen, Phase II.

Sprycel®/dasatinib, Bristol-Myers Squibb, Phase

Tarceva®/erlotinib, Genentech, Phase II.

Telcyta®/canfosfimide, Telik, Phase III.

Tigatuzumab, Daiichi Sankyo, Phase II.

Tykerb®/lapatinib, GlaxoSmithKline, Phase I/II.

Volasertib, Boehringer Ingelheim Pharmaceuticals, Phase II.

Volociximab, Bigen Idec/Facet Biotech, Phase II.

Vosaroxin™/SNS-595, Sunesis Pharmaceuticals, Phase II.

Votrient®/pazopanib, GlaxoSmithKline, Phase III.

Zolinza®/vorinostat, Merck, Phase II.

Zybrestat™/fosbretabulin, OXiGENE, Phase II.

References:

1/The 2011 PhRMA report lists 49 ovarian cancer drugs in development.  After comparing the entire “Cancer” drug list set forth on pages 16 – 24 of the PhRMA report to the ovarian cancer clinical trials provided at http://www.clinicaltrials.gov, we determined that an additional nine drugs appearing on the PhRMA cancer drug list are being tested in ovarian cancer clinical trials.

2/Please note that the PhRMA cancer drug list does not set forth all ovarian cancer drugs in development.  For a list of all open ovarian cancer clinical trials listed at www.clinicaltrials.gov, click here.

Sources:

Resources:

Blunting the Activity of Protein Abcc10 May Help Counter Taxane Drug Resistance In Ovarian Cancer

Posted on by

New findings by Fox Chase Cancer Center researchers identify one protein, Abcc10, as being intimately involved in resistance to certain drugs used to treat breast, ovarian, lung, and other cancers. The results suggest that blunting the activity of Abcc10 might help counter resistance and extend the effectiveness of these anticancer drugs.

Today’s anticancer drugs often work wonders against malignancies, but sometimes tumors become resistant to the effects of such drugs, and treatment fails. Medical researchers would like to find ways of counteracting such resistance, but first they must understand why and how it happens. New findings by Fox Chase Cancer Center researchers identify one protein, Abcc10 (ATP-binding cassette transporter 10) (also known as multidrug resistance protein 7 (Mrp7)), as being intimately involved in resistance to certain drugs used to treat breast, ovarian, lung, and other cancers. The results suggest that blunting the activity of Abcc10 might help counter resistance and extend the effectiveness of these anticancer drugs.

The findings appear in the May 15, 2011 issue of the journal Cancer Research.

Elizabeth A. Hopper-Borge, Ph.D., Assistant Professor, Fox Chase Cancer Center, Philadelphia, Pennsylvania

In earlier work, Elizabeth A. Hopper-Borge, Ph.D., an assistant professor at Fox Chase, showed that Abcc10 confers resistance to a number of anticancer agents, particularly taxanes, which include paclitaxel (Taxol) and docetaxel (Taxotere). These drugs––originally derived from the Pacific yew tree––work by disrupting cell division, thus arresting the growth and spread of tumors. The initial finding that Abcc10, a member of a ubiquitous family of proteins called ATP-binding cassette transporters, thwarts taxanes’ anti-tumor activity was something of a surprise, says Hopper-Borge, because none of the other family members seem to have that ability.

In the new research, Hopper-Borge and colleagues wanted to further explore, in both cultured cells and mice, the role of Abcc10. They developed a “knockout” mouse, in which the gene that codes for Abcc10 was missing, or knocked out. These mice appeared normal and healthy in every other respect, suggesting that Abcc10 is not essential for overall health and survival.

The researchers isolated cells from the knockout mice and tested the cells’ reactions to taxanes and two other anticancer drugs, vincristine and Ara-C. Compared to cells from normal mice that still possessed the gene for Abcc10, the knockout mouse cells were much more sensitive to the drugs.

Abcc10 and its ilk work by pumping drugs out of cells, so one might expect to see the drugs accumulating in cells that lack Abcc10, and that’s exactly what Hopper-Borge’s group saw. It had been suggested that other proteins might take over for Abcc10 if that protein were knocked out, but the researchers found no evidence suggesting that had happened.

Next, the research team studied the effects of one particular taxane, paclitaxel, on mice and found that the knockout mice were more sensitive to the drug, as reflected in body weight, white blood cell count, and ability to survive escalating doses of the drug.

“After seeing the effects on white blood cells, we decided to look at the tissue types that produce white blood cells to see if we could actually see differences there,” says Hopper-Borge. As expected, knockout mice treated with paclitaxel had smaller spleens and thymus glands and underdeveloped bone marrow, compared to normal mice treated with the same drug.

The results provide the first evidence from living organisms that Abcc10 is a cell’s built-in protection against the effects of powerful drugs, and raises the possibility of using Abcc10 inhibitors to break down that resistance and sensitize tumor cells to anticancer agents. The fact that mice lacking the protein have no obvious health problems is encouraging, suggesting that Abcc10 inhibitors could be used in human patients without causing side effects that might be expected to result from interfering with the pump’s normal functions.

Several Abcc10 inhibitors already have been identified, but they also inhibit other cellular transporters, which could have deleterious effects. For that reason, Hopper-Borge thinks the best approach may be developing inhibitors that work only in tumor cells or coming up with compounds that modulate, rather than completely inhibit the protein’s activity.

But using such treatments in patients is still far in the future, she emphasizes.

“I’d like to stress that we did this work in a mouse model,” Hopper-Borge says. “Our results so far suggest that this protein may be a clinically relevant target, but we need to do more studies to find out for sure.”

Co-authors on the study include Timothy Churchill, Chelsy Paulose, Emmanuelle Nicolas, Joely D. Jacobs, Olivia Ngo, Andres J. Klein-Szanto and Martin G. Belinsky of Fox Chase; Yehong Kuang of Central South University, Changsha, China; Alex Grinberg and Heiner Westphal of the National Institute of Child Health and Human Development; and Gary D. Kruh of the University of Illinois at Chicago.

The research was supported by the National Institutes of Health.

Sources:

Libby’s H*O*P*E* & Women’s Oncology Research & Dialogue Launch New “WORD of HOPE™” Ovarian Cancer Educational Podcast Series

Posted on by

WORD OF HOPE™ Ovarian Cancer Podcast Now Available Through New Website, iTunes, YouTube, and Other Online Sources.

A new ovarian cancer educational podcast series, entitled “WORD of HOPE™,” was launched during Women’s Health Awareness Week through a collaborative initiative of Libby’s H*O*P*E*™ (LH) and Women’s Oncology Research & Dialogue (WORD).

The WORD of HOPE™ Ovarian Cancer podcast series will address important topics related to ovarian cancer, including prevention, early detection, diagnosis, groundbreaking treatments, scientific and clinical research information, and related women’s health information for ovarian cancer patients, caregivers and advocates. The WORD of HOPE™ podcast series can be found online at http://www.wordofhopepodcast.com, and is available to viewers and listeners for subscription at the WORD Of HOPE™ podcast website, iTunes, and YouTube.

“From the beginning, WORD has been committed to taking the most important scientific information and providing patients, caregivers and advocates the easily accessible resources to educate and inspire during their journey of care. As a physician, nearly every day we are looking for resources to give newly diagnosed patients and their supporters to help them better understand their diagnosis and treatment options. We are proud to partner with Libby’s H*O*P*E*™ and its founder Paul Cacciatore in the production of these new podcasts,” said Dr. John Geisler, WORD co-founder and Director of Gynecologic Oncology at University of Toledo.

Paul Cacciatore, Libby’s H*O*P*E* founder and podcast co-host said: “The WORD of HOPE™ ovarian cancer podcast series embodies the age old adage that ‘information is power’ — a potentially life-saving concept in the fight against the most lethal gynecologic cancer.” Mr. Cacciatore emphasized that the information featured in the podcast series is easy to understand and accessible from anywhere, including at home, on the job, or on the go through a smartphone or iPad. “WORD of HOPE™ not only raises much-needed ovarian cancer awareness in the minds of the general public, it educates survivors to proactively participate in their treatment through more meaningful dialogue with their doctors. Libby’s H*O*P*E* is proud to partner with WORD through this global form of social media.”

The first podcast installment will feature the following seven episodes (three already posted; four pending) which address ten significant 2010 scientific research and clinical treatment topics within the field of ovarian cancer:

Viewers or listeners of WORD of HOPE™ Ovarian Cancer Podcast can contact Nathan Manahan, WORD Executive Director, via email to provide feedback and ideas for the podcast. To listen, watch or subscribe to the podcast series, visit http://www.wordofhopepodcast.com.

About the WORD of HOPE™ Podcast

Based in Indianapolis, Indiana (WORD) and Los Angeles, California (LH), WORD of HOPE™ serves viewers and listeners interested in up-to-date ovarian cancer information. Hosted by Nathan Manahan and Paul Cacciatore, WORD of HOPE™ ovarian cancer podcasts will be released several times a month and available for subscription through iTunes, RSS and YouTube.

About Women’s Oncology Research & Dialogue

Co-founded by gynecologic oncologists Drs. Kelly Manahan and John Geisler, WORD is an Indianapolis-based nonprofit organization dedicated to helping women conquer gynecologic cancers through catalyzing innovative scientific and clinical research, which results in empowering educational resources for women’s organizations and medical personnel regarding proper prevention, diagnosis and treatment.

About Libby’s H*O*P*E*™

Paul Cacciatore established Libby’s H*O*P*E*(*Helping *Ovarian Cancer Survivors *Persevere Through *Education)™ in March 2008 as an online resource to assist his 26-year-old cousin, Elizabeth “Libby” Remick, who was battling advanced-stage ovarian cancer. Although Libby ultimately lost her battle to the disease, Paul continues to assist ovarian cancer survivors worldwide, and their families and friends, through the website under the principle that “information is power” in the fight against ovarian cancer. Through Libby’s H*O*P*E*™, Paul has published approximately 250 weblog articles relating to ovarian cancer and cancer-related topics. Libby’s H*O*P*E*™ utilizes a variety of online media resources and social networks to disseminate critical information relating to ovarian cancer awareness, including the early warning signs and symptoms of the disease, important medical discoveries, relevant current clinical trials, and most importantly, stories of hope involving ovarian cancer survivors and their families. To learn more, visit https://healthinfoispower.wordpress.com

For more information, contact Executive Producer, Chad Braham at 317-855-8144 or visit the official website: http://www.wordofhopepodcast.com.

OVA1 Blood Test Detects Ovarian Cancer In Women With A Known Ovarian Mass More Accurately Than CA-125

Posted on by

A study published online in Obstetrics & Gynecology reports that the OVA1 blood test detects ovarian cancer in women with a previously discovered ovarian mass more accurately than the CA-125 blood test. The study also considers OVA1’s place in future surgical referral guidelines.

A study published online ahead of print in the June 2011 edition of Obstetrics & Gynecology demonstrated that American College of Obstetrics and Gynecology (ACOG) guidelines for determining the likelihood that an ovarian mass is cancerous prior to surgery would accurately identify more women with ovarian cancer if the OVA1 blood test were used in place of the currently recommended CA-125 (cancer antigen 125) blood test. The study builds on prior research that shows accurate assessment of an ovarian mass for cancer prior to surgery can affect both treatment decisions and health outcomes for women with ovarian cancer.

… When OVA1 was used in place of CA 125 as recommend in the [ACOG] guidelines, 94% of malignancies in women of all ages in the study were accurately detected compared to 77% with CA-125. In addition, OVA1 improved sensitivity in premenopausal women, accurately detecting 91% of women with ovarian cancer in fewer than 58% with CA125. … The study also showed that the OVA1 test was about two times more likely to incorrectly identify women as high risk for ovarian cancer when they were not (a “false positive“) as compared to the CA-125 test overall. … 

OVA1 is the first test cleared by the U.S. Food and Drug Administration (FDA) for aiding in the pre-surgical evaluation of a woman’s ovarian mass for cancer. Vermillion, Inc., a molecular diagnostics company, developed OVA1, and Quest Diagnostics Incorporated, the world’s leading diagnostic testing company, offers OVA1 testing services in the United States and India. Quest Diagnostics and Vermillion both participated in the study and Vermillion also helped fund the study. Neither company had any involvement in the development of the manuscript.

Clinical practice guidelines recommend that women with ovarian cancer be under the care of a gynecologic oncologist, although only an estimated one-third of initial surgeries for ovarian cancer are performed by these specialists. ACOG guidelines for the management of ovarian masses recommend that physicians evaluate several factors, including menopausal status, imaging findings, family history, and CA 125 blood test levels, to divide women into low- and high-risk categories on which treatment plans, including surgical referral, are based.

The study evaluated the performance of the ACOG guidelines using the CA-125 test versus the OVA1 test in 516 women scheduled for surgery for an ovarian mass across a diverse group of primary and specialty care centers. When OVA1 was used in place of CA-125 as recommend in the guidelines, 94% of malignancies in women of all ages in the study were accurately detected compared to 77% with CA 125. In addition, OVA1 improved sensitivity in premenopausal women, accurately detecting 91% of women with ovarian cancer in fewer than 58% with CA-125.

Rachel Ware Miller, M.D., Assistant Professor, Gynecologic Oncology, Markey Cancer Center, University of Kentucky

“The high sensitivity in premenopausal women and early stage cancers is where CA-125 and the College guidelines have underperformed,” wrote investigator Rachel Ware Miller, M.D., assistant professor gynecologic oncology at the University of Kentucky’s Markey Cancer Center, in the study. ” Identifying these patients for referral is valuable because many are not receiving appropriate surgical staging and treatment. An effective preoperative test, particularly for younger women and early-stage cancers, can have a favorable effect on women’s health as survival is better in these populations.”

OVA1 when used with the College guidelines was also effective at detecting advanced disease, when surgery and chemotherapy can “improve overall survival,” wrote Dr. Miller.

The study also showed that the OVA1 test was about two times more likely to incorrectly identify women as high risk for ovarian cancer when they were not (a “false positive“), as compared to the CA-125 test overall. However, as OVA1 is only indicated for women for whom surgery is already planned, a higher rate of false positives would increase the possibility that a woman’s surgery is performed by a gynecologic oncologist rather than a gynecologist or other non-specialist.

The study follows the March 2011 publication in Obstetrics & Gynecology, the official publication of ACOG, of an updated committee opinion, The Role Of The Obstetrician-Gynecologist In The Early Detection Of Epithelial Ovarian Cancer, by ACOG and Society of Gynecologic Oncologists (SGO) that cited the FDA clearance of OVA1 (in 2009) and indicated that OVA1 “appears to improve the predictability of ovarian cancer in women with pelvic masses” and “may be useful for evaluating women with a pelvic mass.”

“Prior to OVA1’s clearance by the FDA, the only lab test physicians could use to assess the likelihood that an ovarian mass was malignant prior to surgery was CA-125, even though CA-125 is not indicated for this use and its performance is variable,” said Dr. Eric T. Fung, chief science officer, Vermillion, Inc. “These data should give physicians more confidence to refer women whose OVA1 test result indicates a high likelihood of cancer to a gynecologic oncologist for surgery.”

Ovarian cancer is the leading cause of death from gynecologic cancers in the United States and the fifth-leading cause of cancer deaths in women. Ovarian masses affect an estimated one million women and lead to as many 300,000 ovarian mass surgeries in the United States each year, according to an analysis by third parties on behalf of Quest Diagnostics.

About OVA1®

OVA1 is the first test cleared by FDA for aiding in the pre-surgical evaluation of a woman’s ovarian mass for cancer, and also is the first protein-based In Vitro Diagnostic Multi-Variate Index Assays (IVDMIA), a new class of state of the art software-based diagnostics. The test utilizes five well-established biomarkers — transthyretin (TT or prealbumin), apoolipoprotein A-1 (Apo A-1), beta 2-microglobulin (beta 2M), transferrin (Tfr) and cancer antigen 125 (CA-125 II) — and proprietary software to determine the likelihood of malignancy in women with ovarian mass for whom surgery is planned.

OVA1 is indicated for women who meet the following criteria: (i) over age 18, (ii) ovarian adnexal mass present for which surgery is planned, and (iii) not yet referred to an oncologist. It is an aid to further assess the likelihood that malignancy is present when the physician’s independent clinical and radiological evaluation does not indicate malignancy. The test should not be used without an independent clinical/radiological evaluation and is not intended to be a screening test or to determine whether a patient should proceed to surgery. Incorrect use of the OVA1 Test carries the risk of unnecessary testing, surgery, and/or delayed diagnosis.

About Quest Diagnostics

Quest Diagnostics is the world’s leading provider of diagnostic testing, information and services that patients and doctors need to make better healthcare decisions. The company offers the broadest access to diagnostic testing services through its network of laboratories and patient service centers, and provides interpretive consultation through its extensive medical and scientific staff. Quest Diagnostics is a pioneer in developing innovative diagnostic tests and advanced healthcare information technology solutions that help improve patient care. Additional company information is available at http://www.questdiagnostics.com/.

About Vermillion, Inc.

Vermillion, Inc. is dedicated to the development and commercialization of novel high-value diagnostic tests that help physicians diagnose, treat and improve outcomes for patients. Vermillion, along with its prestigious scientific collaborators, has diagnostic programs in oncology, cardiology and women’s health. Additional information about Vermillion can be found on the Web at http://www.vermillion.com/.

Sources:

Experimental Drug NVP-BEZ235 Slows Ovarian Cancer Growth in Mice; Solid Tumor Clinical Trials Ongoing

Posted on by

A study conducted recently at UCLA’s Jonsson Comprehensive Cancer Center found that experimental drug NVP-BEZ235, which blocks two points of a crucial cancer cell signaling pathway, inhibits the growth of ovarian cancer cells and significantly increases survival in an ovarian cancer mouse model.

A study conducted recently at  UCLA’s Jonsson Comprehensive Cancer Center (JCCC) found that an experimental drug, which blocks two points of a crucial cancer cell signaling pathway, inhibits the growth of ovarian cancer cells and significantly increases survival in an ovarian cancer mouse model.

Oliver Dorigo, M.D., Ph.D., Assistant Professor, Department of Gynecologic Oncology, Division Gynecologic Oncology, UCLA Jonnson Comprehensive Cancer Center; Member, JCCC Cancer Molecular Imaging Program Area

The Novartis Oncology drug, called NVP-BEZ235, also inhibits growth of ovarian cancer cells that have become resistant to the conventional treatment with platinum chemotherapy and helps to resensitize the cancer cells to the therapy. In addition, it enhances the effect of platinum chemotherapy on ovarian cancer cells that are still responding to the therapy, said the study’s senior author, Dr. Oliver Dorigo, an assistant professor of obstetrics and gynecology and a JCCC researcher.

“Platinum-based chemotherapy drugs are effective in treating ovarian cancers as long as the cancer cells remain sensitive to platinum,” Dorigo said. “But once the tumor becomes resistant, treating the cancer becomes very challenging. This is a significant clinical problem, since the majority of ovarian cancer patients develop resistance at some point during treatment. Breaking chemotherapy resistance is a difficult challenge, but crucial if we want to improve long-term survival for our patients.”

The study, performed on cells lines and mouse models, appears in the April 15 issue of the journal Clinical Cancer Research.

Over the last several years, Dorigo has been working in his laboratory to develop new therapies for ovarian cancer. About 22,000 American women are diagnosed each year with ovarian cancer, and more than 14,000 deaths are attributed to the disease annually. Dorigo has focused his research efforts on a pathway called PI3Kinase/Akt/mTOR, which, once activated, promotes ovarian cancer growth. The activated pathway also makes the cancer more aggressive and more likely to spread to other organs, Dorigo said, so targeting it offers great promise for more effective therapies for the disease.

In this two-year study, Dorigo and postdoctoral fellow Chintda Santiskulvong found that inhibiting two checkpoints of the pathway — PI3Kinase and mTOR — with NVP-BEZ235 decreased cancer growth, both in cell culture dishes and in mice with ovarian cancer. It also significantly increased survival in the mice, he said. More importantly, NVP-BEZ235 slowed growth of the ovarian cancer cells that had become resistant to platinum and helped to break that resistance.

“We were very encouraged to find that NPV-BEZ235 could resensitize the ovarian cancer cells to standard platinum treatment,” Dorigo said. “In addition, we found this drug to be more effective in inhibiting ovarian cancer cell growth than other drugs that target only one checkpoint, mTOR, in this pathway. We believe that NVP-BEZ235 has superior efficacy because of the dual effect on PI3Kinase and mTOR.”

The experimental drug is being tested as a single agent at the Jonsson Cancer Center in human clinical trials against other solid tumors. Researchers involved with those studies have said early results are encouraging.

John Glaspy, M.D., M.P.H., Co-Chief, Department of Medicine, Hematology/Oncology, UCLA Jonnson Comprehensive Cancer Center; JCCC Director, JCCC Clinical Research Unit; Member, Stand Up To Cancer Mangement Committee

“This is clearly a promising agent with activity in humans,” said Dr. John Glaspy, a professor of hematology–oncology and a Jonsson Cancer Center scientist involved with the studies. “We are still assessing its tolerability in patients.”

Dorigo said he hopes to initiate a clinical trial for women with ovarian cancer that tests the combination of NVP-BEZ235 with platinum chemotherapy, as he believes that the combination might be more effective than each drug alone.

The study was funded by the Ovarian Cancer Research Foundation/Liz Tilberis Scholarship, the Gynecologic Cancer Foundation/Florence and Marshall Schwid Ovarian Cancer Award, a STOP Cancer Career Development Award and the National Institutes of Health’s Women’s Reproductive Health Research Program.

About the UCLA Jonnson Comprehensive Cancer Center

UCLA’s Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation’s largest comprehensive cancer centers, the Jonsson Center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2010, the center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 10 of the last 11 years.

Sources:

Clinical Trial Information:

U.K. NICE Issues New Clinical Guidelines Re Recognition & Initial Management of Ovarian Cancer

Posted on by

On April 27, 2011, the U.K. National Institute For Health and Clinical Excellence issued new clinical guidelines regarding the recognition and initial management of ovarian cancer.

On April 27, 2011, the U.K. National Institute For Health and Clinical Excellence (NICE) issued new clinical guidelines regarding the recognition and initial management of ovarian cancer.

In the first ever clinical guideline for ovarian cancer, NICE is calling for more initial investigations to take place in primary care settings, such as general practice (GP) surgeries, so that women can be referred to hospital specialists sooner and begin treatment. This guidance updates and replaces recommendation 1.7.4 in Referral guidelines for suspected cancer (NICE clinical guideline 27; published 2005).

NICE also produced a series of tools to help U.K. healthcare professionals put this new guidance into practice, including guidance documents for doctors and patients, podcasts, clinical case scenarios and a slide set. To view a complete list of all NICE-produced guidance materials available to doctors and patients, visit http://guidance.nice.org.uk/CG122.

The full text NICE ovarian cancer clinical guidelines are classified under the following six chapter headings:

  • Epidemiology
  • Detection in Primary Care
  • Establishing the Diagnosis in Primary Care
  • Management of Suspected Early (stage I) Ovarian Cancer
  • Management of Advanced (stage II-IV) Ovarian Cancer
  • Support Needs of Women With Newly Diagnosed Ovarian Cancer

The key priorities identified by NICE for successful implementation of the new ovarian cancer clinical guidelines by primary and secondary healthcare professionals include the topics addressed below.

Awareness of Symptoms & Signs

— Carry out tests in primary care if a woman (especially if 50 or over) reports having any of the following symptoms on a persistent or frequent basis – particularly more than 12 times per month:

  • persistent abdominal distension (women often refer to this as “bloating”);
  • feeling full (early satiety) and/or loss of appetite;
  • pelvic or abdominal pain; and/or
  • increased urinary urgency and/or frequency.

— Carry out appropriate tests for ovarian cancer in any woman of 50 or over who has experienced symptoms within the last 12 months that suggest irritable bowel syndrome (IBS), because IBS rarely presents for the first time in women of this age.

Asking the Right Question – First Tests

— Measure serum CA125 in primary care in women with symptoms that suggest ovarian cancer.

— If serum CA125 is 35 IU/ml or greater, arrange an ultrasound scan of the abdomen and pelvis.

— For any woman who has normal serum CA125 (less than 35 IU/ml), or CA125 of 35 IU/ml or greater but a normal ultrasound:

  • assess her carefully for other clinical causes of her symptoms and investigate if appropriate; and
  • if no other clinical cause is apparent, advise her to return to her general practitioner (GP) if her symptoms become more frequent and/or persistent.

Malignancy Indices

— Calculate a risk of malignancy index I (RMI I) score (after performing an ultrasound) and refer all women with an RMI I score of 250 or greater to a specialist multidisciplinary team.

— Risk of malignancy index I (RMI I): RMI I is a product of the ultrasound scan score (U), menopausal status (M) and serum CA125 level.

— RMI I = U x M x  CA125

  • The ultrasound result is scored 1 point for each of the following characteristics: multilocular cysts, solid areas, metastases, ascites, and bilateral lesions. U = 0 for an ultrasound score of 0 points, U = 1 for an ultrasound score of 1 point, U = 3 for an ultrasound score of 2–5 points.
  • Menopausal status is scored as 1 = pre-menopausal and 3 = post-menopausal. The classification of “post-menopausal” is a woman who has had no period for more than 1 year or a woman over 50 who has had a hysterectomy.
  • Serum CA125 is measured in IU/ml.

Tissue Diagnosis

— If offering cytotoxic chemotherapy to women with suspected advanced ovarian cancer, first obtain a confirmed tissue diagnosis by histology (or by cytology if histology is not appropriate) in all but exceptional cases.

The Role of Systematic Retroperitoneal Lymphadenectomy

— Do not include systematic retroperitoneal lymphadenectomy (block dissection of lymph nodes from the pelvic side walls to the level of the renal veins) as part of standard surgical treatment in women with suspected ovarian cancer whose disease appears to be confined to the ovaries (that is, who appear to have stage I disease).

Adjuvant Systemic Chemotherapy For Stage I Disease

— Do not offer adjuvant chemotherapy to women who have had optimal surgical staging and have low-risk stage I disease ([tumor] grade 1 or 2, stage Ia or Ib).

Support Needs of Women with Newly Diagnosed Ovarian Cancer

— Offer all women with newly diagnosed ovarian cancer information about their disease, including psychosocial and psychosexual issues, that:

  • is available at the time they want it;
  • includes the amount of detail that they want and are able to deal with; and
  • is in a suitable format, including written information.

Source:  Ovarian cancer: the recognition and initial management of ovarian cancer (CG122), Full Guideline, National Institute For Health & Clinical Excellence (NICE), U.K. National Health Service (NHS), April 2011.

Additional Information:

2011 AACR Annual Meeting: Select Ovarian Cancer Presentations & Abstracts Available Online

Posted on by

The 102nd American Association For Cancer Research (AACR) Annual Meeting will be held from Saturday, April 2 through Wednesday, April 6, 2011, at the Orange County Convention Center located in Orlando, Florida.  Select ovarian cancer presentations and abstracts are available online.

The 102nd American Association For Cancer Research (AACR) Annual Meeting will be held from Saturday, April 2 through Wednesday, April 6, 2011, at the Orange County Convention Center located in Orlando, Florida.  Select ovarian cancer meeting presentations and abstracts are now available online.

Once again, the AACR will host and organize an exciting program on the best and latest in cancer research, in which a large cross section of the cancer research community will participate, to advance the cause of treating and preventing cancer. The meeting program not only reflects the AACR’s strengths in basic, translational, and clinical research, but also emphasizes the productive interfaces emerging between these once-separated disciplines. The program also captures the advances on all of these fronts, with a range of speakers and participants who are leaders in research: cancer mechanisms, systems approaches to cancer biology, diagnostics and therapeutics, translation of advances to the clinic, and cutting-edge science in the prevention and early interception of cancer.

In advance of the actual meeting, you can review select ovarian cancer meeting and poster presentations that relate to basic, clinical, epidemiological, and translational research.

To view all available ovarian cancer meeting and poster presentations, CLICK HERE, and then click the “advanced search button,” and under “Abstract Organ Site,” choose “gynecological cancer:  ovarian cancer,” then click “search” at the top or bottom of the page .

To view a list of all available AACR program ovarian cancer-related webcasts available during and/or after the meeting, CLICK HERE and (i) type in “ovarian cancer” in the search box; (ii) choose “sessions (with details)” under the “Browse By” menu at the top of the page; and (iii) choose only “2011” within the  search filter (i.e., uncheck conference years 2004 – 2010), then click “Update Filter.” (note: you can also search for free and/or paid webcasts by using the search filter on this page).

Libby’s H*O*P*E*™ will post newsworthy ovarian cancer information that is disclosed during the course of the AACR Annual Meeting.

About the American Association For Cancer Research

The mission of the American Association for Cancer Research is to prevent and cure cancer. AACR was founded in 1907 by a group of 11 physicians and scientists interested in research “to further the investigation and spread the knowledge of cancer.” The AACR is the world’s oldest and largest professional organization dedicated to advancing cancer research. The membership includes 33,000 basic, translational and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 90 other countries.

The AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants, research fellowships and career development awards. The AACR Annual Meeting attracts more than 18,000 participants who share the latest discoveries and developments in the field. Special conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment and patient care. Including Cancer Discovery, the AACR publishes seven major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; Cancer Epidemiology, Biomarkers & Prevention; and Cancer Prevention Research. AACR journals represented 20 percent of the market share of total citations in 2009. The AACR also publishes CR, a magazine for cancer survivors and their families, patient advocates, physicians and scientists.

Phenoxodiol Used In Combination With Platinum or Taxane-Based Chemotherapy Is Active In Platinum & Taxane-Resistant Ovarian Cancer

Posted on by

Phase II clinical study results suggests phenoxodiol is active in platinum and taxane drug-resistant ovarian cancer patients when administered intravenously in combination with platinum or taxane-based chemotherapy

Marshall Edwards, Inc., an oncology company focused on the clinical development of novel therapeutics targeting cancer metabolism, recently announced the publication of results from a phase II clinical trial of intravenous phenoxodiol in combination with cisplatin or paclitaxel in women with platinum–refractory/resistant ovarian cancer. The publication is now available on the International Journal of Gynecological Cancer website, and the print edition will appear the May issue of the journal.

The study, conducted at Yale-New Haven Hospital, showed that the combination of intravenous phenoxodiol, a novel NADH oxidase inhibitor, with cisplatin (a platinum-based chemotherapy) or paclitaxel (a taxane-based chemotherapy), was well tolerated.

Robert D. Mass, M.D., Acting Chief Medical Officer, Marshall Edwards.

In the study, 32 patients were randomized to one of two treatment arms according to their previous treatment responses: (1) platinum refractory/resistant patients received weekly cisplatin (40 mg/m intravenous), combined with weekly phenoxodiol (3 mg/kg); and (2) taxane refractory/resistant patients received weekly paclitaxel (80 mg/m intravenous), combined with weekly phenoxodiol (3 mg/kg). The study patients continued on treatment until complete response, disease progression, unacceptable toxicity, or voluntary withdrawal.

In the cisplatin study arm, there were 3 partial responses, 9 patients (56%) achieved stable disease, 4 patients (25%) progressed, and the overall best response rate was 19%. In the paclitaxel study arm, there was one complete response and 2 partial responses, 8 patients (53%) achieved stable disease, 4 patients (27%) progressed, and the overall best response rate was 20%. Response rate in this study was defined as the percentage of patients whose tumor demonstrated a radiologically confirmed reduction or disappearance after treatment.

There were no treatment-related deaths in the study, and there was only one treatment-related hospitalization and two grade 4 (i.e., life-threatening or disabling) adverse events.

Based upon the foregoing results, the researchers concluded that the combination of intravenous phenoxodiol with cisplatin or paclitaxel was well tolerated.  Moreover, the researchers stated that the cisplatin-phenoxodiol combination was particularly active and warrants further study in patients with platinum-resistant ovarian cancer.

“These results suggest that the combination of intravenous phenoxodiol with cisplatin has a good safety profile and may be capable of reversing resistance to platinum-based chemotherapy,” said lead author Michael G. Kelly, M.D., a gynecologic oncologist at Tufts Medical Center and former fellow at Yale University School of Medicine.” This study provides early clinical proof-of-concept for the combination of NADH oxidase inhibitors with standard-of-care chemotherapy and lays the groundwork for the development of more potent next-generation compounds.”

To date, phenoxodiol, an investigational drug, has been introduced into more than 400 patients in multiple clinical trials via oral or intravenous routes and has been well tolerated. Marshall Edwards has identified a next-generation compound called “NV-143,” which has demonstrated significantly more activity than phenoxodiol against a broad range of tumor cell lines. In addition to being more active as a single agent, NV-143 appears to be superior in its ability to synergize with platinum-based chemotherapy in pre-clinical studies. As a result, Marshall Edwards plans to initiate a phase I clinical trial of intravenous NV-143 later this year, followed immediately thereafter by randomized phase II trials in combination with chemotherapy.

“These published results combined with data from previous studies reinforce our conclusion that intravenous administration is the optimal route of delivery for this class of drugs and give us added confidence moving forward as we develop our next-generation compound NV-143 for the clinic,” said Robert D. Mass, M.D., Acting Chief Medical Officer of Marshall Edwards.

About Marshall Edwards

Marshall Edwards, Inc. is a San Diego-based oncology company focused on the clinical development of novel anti-cancer therapeutics. The Company’s lead programs focus on two families of small molecules that result in the inhibition of tumor cell metabolism. The first and most advanced is a NADH oxidase inhibitor program that includes lead drug candidate NV-143. The second is a mitochondrial inhibitor program that includes NV-128 and its next-generation candidate NV-344. Both programs are expected to advance into the clinic in 2011. For more information, visit www.marshalledwardsinc.com.

About Novogen Limited

Novogen Limited is an Australian biotechnology company based in Sydney, Australia. Novogen has a consumer healthcare business, and conducts research and development on oncology therapeutics through its 71.3% owned subsidiary, Marshall Edwards, Inc.

Sources:

Therapeutic Response To The Angiogenesis Inhibitor Sunitinib In Ovarian Clear Cell Cancer

Posted on by

A group of international researchers reported sustained responses in two ovarian clear cell cancer (OCCC) patients with chemotherapy-resistant disease, who were treated with the anti-angiogenesis inhibitor sunitinib (Sutent®). The researchers emphasize the growing realization that OCCC is molecularly and clinically distinct as compared to other forms of ovarian cancer, and note significant common scientific characteristics possessed by both OCCC and renal clear cell cancer.

Clear Cell Carcinoma of the Ovary

Ovarian clear cell cancer (OCCC) is a rare form or subtype of epithelial ovarian cancer that is generally refractory to platinum-based chemotherapy. A group of international researchers from the United Kingdom, Australia, Japan, Canada and the United States recently reported results from comprehensive OCCC tumor gene expression and copy number testing, which was designed to identify potential therapeutic targets of OCCC.

Gene expression and DNA copy number testing was performed using primary human OCCC tumor samples, and the test findings were confirmed by immunohistochemistry (IHC) on tissue microarrays. Based on this testing, the researchers identified specific over-expression of the IL6 (interleukin-6)-STAT3 (signal transducer and activator of transcription 3)-HIF (hypoxia-inducible factors) cellular pathway in OCCC tumors, as compared with high-grade serous ovarian cancers. Expression of PTHLH (parathyroid hormone-like hormone) and high levels of circulating IL6 were also found in OCCC patients, and the researchers believe that this finding may explain the frequent occurrence of hypercalcemia and thromboembolic events in OCCC. Notably, the study results set forth a description of amplification of several RTKs (receptor tyrosine kinases), most notably MET (met proto-oncogene [hepatocyte growth factor receptor]), which certainly suggests other potential therapeutic targets for this hard-to-treat subtype of ovarian cancer.

Circulating IL6 levels were measured in the blood serum from patients with OCCC or high-grade serous ovarian cancers and corresponded to progression-free and overall survival. Two OCCC patients were treated with sunitinib and their therapeutic responses were measured clinically and by positron emission tomography (PET). The researchers reported sustained clinical and functional imaging responses in two OCCC patients with chemotherapy-resistant disease who were treated with sunitinib, thereby showing  significant scientific parallels with renal clear cell cancer.

Based upon the findings above, the researchers highlighted the importance of specific therapeutic targets in the treatment of OCCC, and suggested that more extensive clinical trials with sunitinib in OCCC patients are warranted.  The overarching findings of this study provide significant impetus to the growing realization that OCCC is molecularly and clinically distinct as compared to other forms of ovarian cancer.

Source: Anglesio MS, George J, Kulbe H, et. al. IL6-STAT3-HIF Signalling and Therapeutic Response To The Angiogenesis Inhibitor, Sunitinib, In Ovarian Clear Cell Cancer. Clin Cancer Res. 2011 Feb 22. [Epub ahead of print] PubMed PMID: 21343371.

Additional Information:

  • Dedicated Ovarian Clear Cell Cancer Clinical Trials (currently recruiting as of 3/25/11).

A Phase II Evaluation of SU11248 (Sunitinib Malate) (IND #74019, NSC #736511) in the Treatment of Persistent or Recurrent Clear Cell Ovarian Carcinoma, Clinical Trial Summary, NCT00979992, ClinicalTrials.gov.

A Phase II Evaluation of Temsirolimus (CCI-779) [Torisel®] (NCI Supplied Agent: NSC# 683864, IND# 61010) in Combination With Carboplatin and Paclitaxel Followed by Temsirolimus (CCI-779) Consolidation as First-Line Therapy in the Treatment of Stage III-IV Clear Cell Carcinoma of the Ovary, Clinical Trial Summary, NCT01196429, ClinicalTrials.gov.

  • Open Ovarian Cancer and Solid Tumor Clinical Trials Testing MET Inhibitors (as of 3/25/11)

We provide below a list of MET inhibitors that are currently available through open ovarian cancer and solid tumor clinical trials.  A few caveats are noteworthy.

First, the association between MET inhibiton and ovarian clear cell cancer inhibition has NOT been established as a form of treatment in large randomized, prospective clinical trials.

Second, most of the clinical trials listed below are phase I studies designed to test the biological activity and safety of the drug — not the effectiveness.  Patients enrolled in a phase I trial are generally the first humans to receive the study drug.

Third, all patients should seek advice from their doctor in advance of deciding to enroll in a clinical trial. Many of the clinical drugs listed below inhibit one or more cellular functions in addition to MET.

List of open solid tumor clinical trials testing AMG 208.

List of open solid tumor clinical trials testing MGCD-265.

List of open solid tumor clinical trials testing PF-2341066 (crizotinib)(NCT01121588 & NCT00585195).

List of open ovarian cancer clinical trials testing sunitinib (SU11274)/Sutent®.

List of open solid tumor clinical trials testing sunitinib (SU11274)/Sutent®.

List of open solid tumor clinical trials testing cabozantinib (a/k/a XL184 or BMS-907351).

List of open solid tumor clinical trials testing ARQ197.

List of open solid tumor clinical trials testing INCB28060.

List of open solid tumor clinical trials testing E7050.

List of open solid tumor clinical trials testing MGCD265.

  • Genetic Similarity Between Ovarian Clear Cell Cancer & Renal Clear Cell Cancer

Yoshida S, Furukawa N, Haruta S, et. al. Theoretical model of treatment strategies for clear cell carcinoma of the ovary: focus on perspectives. Cancer Treat Rev. 2009 Nov;35(7):608-15. Epub 2009 Aug 8. Review. PubMed PMID: 19665848.

Rauh-Hain JA, Penson RT. Potential benefit of Sunitinib in recurrent and refractory ovarian clear cell adenocarcinoma. Int J Gynecol Cancer. 2008 Sep-Oct;18(5):934-6. Epub 2007 Dec 13. PubMed PMID: 18081793.

Zorn KK, Bonome T, Gangi L, et. al. Gene expression profiles of serous, endometrioid, and clear cell subtypes of ovarian and endometrial cancer. Clin Cancer Res. 2005 Sep 15;11(18):6422-30. PubMed PMID: 16166416.

“If You Are Lucky Enough To Be Irish, Then You Are Lucky Enough”

Posted on by

Based on the Irish saying set forth above, I am certainly lucky enough — at least half of me is, on my mom’s side of the family.

All things Irish in celebration of St. Patrick's Day. (Photo: ShannonPatrick17)

Based on the Irish saying set forth above, I am certainly lucky enough — at least half of me is, on my mom’s side of the family.  For those of you who were “lucky enough” to be raised by one or two Irish parents, you know what I’m talking about — faith, family, cultural pride, education (Notre Dame, of course), food and drink (with an emphasis on drink), and good old fashion storytelling.

May the blessings of each day be the blessings you need most. — Irish proverb

My mother and one of my best friends (and former college roommate) provided me with my formal education of all things Irish. In fact, when we were in college, my roommate Sean referred to St. Patrick’s Day as the “holiest of holy days” — needless to say, nothing has changed since college.  He considers himself to be “very lucky” because he was raised by two Irish parents. In fact, Sean is so Irish that he founded a highly successful Irish dancing school in 1997 called, The Culkin School of Traditional Irish Dance, which is located in the Washington, D.C. area. Sean’s students have performed at many famous venues, including The John F. Kennedy Center for the Performing Arts.

Stephen: [looking to the sky] Alright, Father, I’ll ask him. …

Hamish: Is your father a ghost, or do you converse with the Almighty?

Stephen: In order to find his equal, an Irishman is forced to talk to God.

— Dialogue from the movie Braveheart (1995 Academy Award-Winning Best Picture).

If you live in an Irish household, today will likely involve a few traditions such as wearing green (bonus points for wearing a lapel pin with an image of a shamrock, Irish flag, or leprechaun); eating corned beef, cabbage, and soda bread; and drinking Guinness stout.  If you know nothing of Ireland, you can “fake it till you make it,” by going to a local Irish pub, or by learning a few fun facts related to St. Patrick’s Day and Irish Americans.

  • St. Patrick’s Day is celebrated on March 17, his religious feast day and the anniversary of his death in the 5th century. The Irish have observed this day as a religious holiday for over a thousand years.
  • The shamrock, which was also called the “seamroy” by the Celts, was a sacred plant in ancient Ireland because it symbolized the rebirth of spring.  By the 17th century, the shamrock had become a symbol of emerging Irish nationalism.
  • Music is often associated with St. Patrick’s Day and Irish culture in general. From the ancient days of the Celts, music has always been an important part of Irish life. The Celts had an oral culture, where religion, legend and history were passed from one generation to the next by way of stories and songs.
  • It has long been recounted that during his mission in Ireland, St. Patrick once stood on a hilltop (which is now called Croagh Patrick) with only a wooden staff by his side, and banished all the snakes from the island. In fact, the island nation was never home to any snakes. The “banishing of the snakes” was really a metaphor for the eradication of pagan ideology from Ireland and the triumph of Christianity. Within 200 years of Patrick’s arrival, Ireland was completely Christianized.
  • In 1959, Walt Disney released a film called Darby O’Gill & the Little People, which introduced America to a very different sort of leprechaun, as compared to the cantankerous little man of Irish folklore. This cheerful, friendly leprechaun is a purely American invention, but has quickly evolved into an easily recognizable symbol of both St. Patrick’s Day and Ireland in general.
  • Though cabbage has long been an Irish food, corned beef only began to be associated with St. Patrick’s Day at the turn of the 20th century. Irish immigrants living on New York City’s Lower East Side substituted corned beef for their traditional dish of Irish bacon to save money.
  • The Irish are not required to be Boston Celtics fans — go with a winner and side with the Los Angeles Lakers. (Sorry, that’s commentary rather than fact!)
  • When the Great Potato Famine hit Ireland in 1845, close to a million poor and uneducated Irish Catholics began pouring into the U.S. to escape starvation.
  • There are 36.9 million U.S. residents with Irish roots. This number is more than eight times the population of Ireland itself (4.5 million).
  • Across the U.S., 12 percent of residents lay claim to Irish ancestry. That number doubles to 24 percent in the state of Massachusetts.
  • The first St. Patrick’s Day parade took place in the U.S., not in Ireland. Irish soldiers serving in the English military marched through New York City on March 17, 1762.
  • The New York City St. Patrick’s Day Parade is the world’s oldest civilian parade and the largest in the U.S., with over 150,000 participants.
  • Chicago is famous for a somewhat peculiar St. Patrick’s Day annual event: dyeing the Chicago River green. The tradition started in 1962, when city pollution-control workers used dyes to trace illegal sewage discharges and realized that the green dye might provide a unique way to celebrate the holiday. That year, they released 100 pounds of green vegetable dye into the river—enough to keep it green for a week!  Today, in order to minimize environmental damage, only 40 pounds of dye are used, making the river green for only several hours.

I would like to take this opportunity to wish my mom (and her sisters) and the Culkin family all the best on this special day.  At Libby’s H*O*P*E*, we also wish you and yours a Happy St. Patrick’s Day.

May you always walk in sunshine. May you never want for more. May Irish angels rest their wings right beside your door.

–Irish Blessing

In the tradition of Irish music on St. Patrick’s Day, we leave you with a song by the Irish-American band Flogging Molly, entitled If I Ever Leave This World Alive.  This song is dedicated to those women who have lost their battle to ovarian cancer, but who inspire us to continue the fight for, and support of, ovarian cancer survivors and their families.

If I Ever Leave This World Alive, by Flogging Molly

2011 NCCN Conference: New Treatment Options Lead to Steady Progress Against Ovarian Cancer

Posted on by

Recommendations stemming from recent clinical trials highlight notable updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™) for Ovarian Cancer at the National Comprehensive Cancer Network® (NCCN®) 16th Annual Conference.

Robert J. Morgan, Jr., M.D., Professor of Medical Oncology, City of Hope Comprehensive Cancer Center; Chair, NCCN Guidelines Panel for Ovarian Cancer

Although finding effective screening tools remains a priority, new treatment options for women with ovarian cancer, such as the ones outlined in the updated NCCN Guidelines for Ovarian Cancer,[1] are vital to making steady progress against the disease according to Robert J. Morgan, Jr., M.D., of City of Hope Comprehensive Cancer Center and chair of the NCCN Guidelines Panel for Ovarian Cancer. Dr. Morgan outlined significant updates to the NCCN Guidelines during a recent presentation at the NCCN 16th Annual Conference.

The NCCN Guidelines address epithelial ovarian cancer (including borderline or low malignant potential) and less common histopathologies, including malignant germ neoplasms, carcinosarcomas, and sex cord-stromal tumors. They also discuss fallopian tube cancer and primary peritoneal cancer, which are less common neoplasms that are managed in a similar manner to epithelial ovarian cancer.

“Regardless of the type of cancer, the NCCN Guidelines for Ovarian Cancer reflect the importance of stage and grade of disease on prognosis and treatment recommendations,” said Dr. Morgan.

The NCCN Guidelines continue to recommend that women with borderline epithelial ovarian cancer of low malignant potential be primarily surgically managed. In contrast to patients with frankly invasive ovarian carcinoma, women with borderline disease tend to be younger and are often diagnosed with stage I disease.

“The benefits of postoperative chemotherapy has not been demonstrated for patients who have no microscopically demonstrable invasive implants, said Dr. Morgan. “Even patients with advanced stage disease at presentation have an excellent prognosis and chemotherapy should be avoided.”

The NCCN Guidelines recommend surgery limited to a unilateral salpingo-oophorectomy (USO) (preserving the uterus and contralateral ovary) for women who wish to maintain their fertility, and standard ovarian cancer debulking surgery is recommended for those not concerned about fertility preservation.

On the contrary, in women diagnosed with stage II, III, or IV epithelial ovarian cancer, the NCCN Guidelines recommend intraperitoneal chemotherapy for first-line therapy and have been updated to include dose-dense paclitaxel (Taxol®:, Bristol-Myers Squibb) as a possible treatment option.

Dr. Morgan noted that in a recent clinical trial, dose-dense weekly paclitaxel with carboplatin (Paraplatin®:, Bristol-Myers Squibb) showed an increase in both progression-free survival and overall survival when compared with conventional intraperitoneal chemotherapy of weekly carboplatin/paclitaxel.[2]

“However, the dose-dense regimen is more toxic, and patients discontinued dose-dense paclitaxel therapy more often than those receiving standard therapy,” stated Dr. Morgan. “As with all treatment decisions, the patient needs to weigh the potential benefits and risks and discuss them thoroughly with their physician.”

Dr. Morgan discussed two additional phase 3 trials assessing bevacizumab (Avastin®:, Genentech/Roche) combined with carboplatin/paclitaxel in the upfront setting compared to carboplatin/paclitaxel alone.[3-4] Although data regarding overall survival and quality of life have not been reported yet, the studies did indicate that the median progression-free survival increased in patients receiving bevacizumab as a first line and maintenance therapy.

“Only modest improvements in progression-free survival were observed in both of these trials. The NCCN Guidelines Panel prefers to await mature results of these trials prior to recommending the routine addition of bevacizumab to carboplatin/paclitaxel,” said Dr. Morgan.

As such, the updated NCCN Guidelines includes new language detailing the Panel’s view on bevacizumab encouraging participation in ongoing clinical trials that are further investigating the role of anti-angiogenesis agents in the treatment of ovarian cancer, both in the upfront and recurrence settings.

Biomarkers continue to emerge as an area of interest in predicting future patterns of the disease. In patients with ovarian cancer, Dr. Morgan discussed the value of monitoring CA-125 levels in regards to a recent study[5] comparing early versus delayed treatment of relapsed ovarian cancer.

“Often, levels of CA-125 have been shown to rise prior to a clinical or symptomatic relapse in women with ovarian cancer. This trial looked at whether there was a benefit of early treatment on the basis of increased CA-125 concentrations compared with delayed treatment on the basis of clinical recurrence,” said Dr. Morgan.

The study, which was published in The Lancet, found that there was no survival benefit to early institution of treatment based on increased CA-125 levels and that the quality of life was superior in patients in the late treatment arm.

“The results of the trial suggest that the utility of the routine monitoring of CA-125 levels in limited,” said Dr. Morgan. “The NCCN Guidelines Panel encourages patients and their physicians to actively discuss the pros and cons of CA-125 monitoring based upon these findings and have updated the NCCN Guidelines to include language supporting this recommendation.”

Virtually all drugs used in oncology have the potential to cause adverse drug reactions while being infused, which can be classified as either infusion or allergic reactions. Recently, hypersensitivity to platinum compounds has been recognized as a potential issue for patients being administered these compounds.

“Platinum compounds remain very important in the treatment of ovarian cancer in both the upfront and recurrence settings, so it was important to design strategies to allow for the safe desensitization of these agents in patients who develop allergies,” said Dr. Morgan.

Standard desensitization regimens include slowly increasing infusion concentrations over several hours. However, Dr. Morgan noted that these procedures must be done in a specific manner in order to be safely administered and pointed to the recommendations within the updated NCCN Guidelines discussing the management of drug reactions.

In conclusion, Dr. Morgan emphasized that although steady progress is being made in the treatment of ovarian cancer, further trials are necessary to investigate the role of targeted agents alone and in combination in newly diagnosed and recurrent ovarian cancer. In addition, enrollment of patients with ovarian cancer must be encouraged.

The NCCN Guidelines are developed and updated through an evidence-based process with explicit review of the scientific evidence integrated with expert judgment by multidisciplinary panels of expert physicians from NCCN Member Institutions. The most recent version of this and all NCCN Guidelines are available free of charge at NCCN.org. The NCCN Guidelines for Patients™: Ovarian Cancer is available at NCCN.com.

About the National Comprehensive Cancer Network

The National Comprehensive Cancer Network® (NCCN®), a not-for-profit alliance of 21 of the world’s leading cancer centers, is dedicated to improving the quality and effectiveness of care provided to patients with cancer. Through the leadership and expertise of clinical professionals at NCCN Member Institutions, NCCN develops resources that present valuable information to the numerous stakeholders in the health care delivery system. As the arbiter of high-quality cancer care, NCCN promotes the importance of continuous quality improvement and recognizes the significance of creating clinical practice guidelines appropriate for use by patients, clinicians, and other health care decision-makers. The primary goal of all NCCN initiatives is to improve the quality, effectiveness, and efficiency of oncology practice so patients can live better lives. For more information, visit NCCN.org.

The NCCN Member Institutions are:

  • City of Hope Comprehensive Cancer Center
  • Dana-Farber/Brigham and Women’s Cancer Center
  • Massachusetts General Hospital Cancer Center
  • Duke Cancer Institute
  • Fox Chase Cancer Center
  • Huntsman Cancer Institute at the University of Utah
  • Fred Hutchinson Cancer Research Center / Seattle Cancer Care Alliance
  • The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
  • Robert H. Lurie Comprehensive Cancer Center of Northwestern University
  • Memorial Sloan-Kettering Cancer Center
  • H. Lee Moffitt Cancer Center & Research Institute
  • The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute
  • Roswell Park Cancer Institute
  • Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine
  • St. Jude Children’s Research Hospital / University of Tennessee Cancer Institute
  • Stanford Comprehensive Cancer Center
  • University of Alabama at Birmingham Comprehensive Cancer Center
  • UCSF Helen Diller Family Comprehensive Cancer Center
  • University of Michigan Comprehensive Cancer Center
  • UNMC Eppley Cancer Center at The Nebraska Medical Center
  • The University of Texas MD Anderson Cancer Center
  • Vanderbilt-Ingram Cancer Center

References:

1/ Ovarian Cancer Including Fallopian Tube Cancer & Primary Peritoneal Cancer, Version 2.2011, NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™), National Comprehensive Cancer Network. [PDF Adobe Reader Document – requires free registration and log-in at NCCN.org]

2/ Katsumata N, Yasuda M, Takahashi F, et. al. Japanese Gynecologic Oncology Group. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009 Oct 17;374(9698):1331-8. Epub 2009 Sep 18. PubMed PMID: 19767092.

3/ Burger RA, Brady MF, Bookman MA, et. al.  Phase III trial of bevacizumab in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC):  a Gynecologic Oncology Group study.  J Clin Oncol 28:18s, 2010 (suppl; abstr LBA1).

4/ Perren T, Swart AM, Pfisterer J, et. al. ICON7: A phase III randomized gynecologic cancer intergroup trial of concurrent bevacizumab and chemotherapy followed by maintenance bevacizumab, versus chemotherapy alone in women with newly diagnosed epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC).Ann Oncol 21;viii2, 2010 (suppl 8; abstr LBA4).

5/Rustin G, van der Burg M, Griffin C, et. al. Early versus delayed treatment of relapsed ovarian cancer. Lancet. 2011 Jan 29;377(9763):380-1. PubMed PMID: 21277438.

Source:

Additional 2011 NCCN Annual Meeting Information

Ohio State University Reports That Ovarian Cancer Drug Bevacizumab Is Not Cost-Effective

Posted on by

An analysis conducted by Ohio State University cancer researchers found that adding the targeted therapy bevacizumab to the first-line treatment of patients with advanced ovarian cancer is not cost effective.

An analysis conducted by Ohio State University cancer researchers found that adding the targeted therapy bevacizumab [Avastin®] to the first-line treatment of patients with advanced ovarian cancer is not cost-effective.

The findings comparing the relative value of various clinical strategies were published online March 7 in the Journal of Clinical Oncology (JCO).

Dr. David E. Cohn is a gynecologic oncologist & researcher at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital & Richard J. Solove Research Institute. He is also the lead author of the bevacizumab cost-effectiveness study.

The researchers performed a cost-effectiveness analysis looking at a clinical trial conducted by the Gynecologic Oncology Group (GOG) studying the use of bevacizumab along with standard chemotherapy for patients with advanced ovarian cancer, said first author Dr. David E. Cohn, a gynecologic surgical oncologist and researcher at The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James).

Bevacizumab is a novel targeted therapy designed to inhibit angiogenesis, the process by which new blood vessels develop and carry vital nutrients to a tumor.

Although a discussion regarding cost-effectiveness of a potentially life-extending intervention invariably suggests the rationing of limited health care resources, the intent of this study was to provide a framework with which to evaluate the pending results of a clinical trial of three different interventions for ovarian cancer, said Cohn.

“We do not suggest that bevacizumab, also known by the brand name Avastin, should be withheld from a patient with ovarian cancer, but rather argue that studies evaluating the effectiveness of new treatments should also be interpreted with consideration of the expense,” says Cohn, who collaborated with Dr. J. Michael Straughn Jr., an associate professor of obstetrics and gynecology at the University of Alabama at Birmingham.

The results of the randomized phase III [GOG 218] clinical trial demonstrated an additional 3.8 months of progression-free survival (PFS) when maintenance bevacizumab was added for about one year following treatment with standard chemotherapy drugs carboplatin and paclitaxel along with bevacizumab.

“We put together a model looking at the variety of treatment arms on this clinical trial, each of which included 600 patients,” said Cohn. “Given the fact that the addition of the drug was associated with 3.8 months of additional survival without cancer, we set out to determine whether or not that benefit of survival was justified by the expense of the drug.”

The model showed that standard chemotherapy for patients in the clinical trial would cost $2.5 million, compared to $78.3 million for patients who were treated with standard chemotherapy and bevacizumab, plus additional maintenance treatments of bevacizumab for almost one year.

Bevacizumab has been used in the treatment of recurrent ovarian cancer, and the U.S. Food and Drug Administration has approved it for the treatment of colorectal, lung, breast, brain (glioblastoma) and renal cell [kidney] cancers.

Typically each treatment with bevacizumab costs $5,000, with most of those costs directly attributable to the cost of the drug, Cohn said.

Effectiveness was defined as months of progression-free survival, and costs were calculated as total costs per strategy. Cost-effectiveness strategies were defined as the cost per year of progression-free survival. Incremental cost-effectiveness ratio was defined as the costs per progression-free year of life saved.

“Ultimately, we found that if you reduced the drug cost to 25 percent of the baseline, it does become cost effective to treat patients with bevacizumab,” said Cohn. “Or, if the survival could be substantially increased above the 3.8 months of progression-free survival, that could lead to cost-effective treatment for patients with advanced ovarian cancer.”

Ovarian cancer is the most lethal gynecologic cancer, with almost 14,000 women expected to die from the disease this year, according to the American Cancer Society.

“It is anticipated that in the future, there will be increased scrutiny regarding the individual and societal costs of an effective medication,” said Cohn. “We hope that future clinical trials will incorporate the prospective collection of cost, toxicity and quality-of-life data to allow for a fully informed interpretation of the results.”

Other Ohio State researchers involved in the study are Kenneth H. Kim, Kimberly E. Resnick and David O’Malley.

Big Cost For Little Gain in Ovarian Cancer – JCO Editorial

Results of the cost-effectiveness model reported above by Cohen et. al. reveal that paclitaxel plus carboplatin plus bevacizumab, followed by bevacizumab maintenance (PCB-B), as tested in the GOG 218 phase III clinical trial, costs $78.3 million ($1,305,000 per patient) with an incremental cost-effectiveness ratio of $401,088 per progression-free year of life saved. It is important to note that traditional cost-effectiveness study models utilize the costs of improvements in overall survival, as compared to the traditional cost-effective standard of $50,000 per year of life saved, or more recently, $100,000 per year of life saved.  Cohen et. al. found that the traditional standard of $100,000 per progression free year of life saved can be achieved in calculating the incremental cost-effectiveness ratio, but only at a bevacizumab drug price point that is 25% below the actual drug cost.

Martee L. Hensley, M.D., Gynecologic Medical Oncology Service, Memorial Sloan-Kettering Cancer Center

In an accompanying JCO editorial, Martee L. Hensley, M.D., a board-certified medical oncologist who treats women with gynecologic cancers at the Memorial Sloan-Kettering Cancer Center in New York city, raises several important considerations with respect to the Ohio State University study.

First, Dr. Hensley notes that the “costs” accounted for by the Ohio State University researchers only refer to the additional monies incurred by adding bevacizumab to the standard of care paclitaxel-carboplatin treatment.  Specifically, the researchers used a standard cost metholodolgy based upon estimates of drug costs using Medicare reimbursement rates.  The model used does not include indirect costs (e.g., patient out-of-pocket expenses, time lost from work associated with 51 weeks of bevacizumab maintenance, etc.). The only costs related to toxicity of treatment included by researchers were those associated with management of intestinal perforations. Dr. Hensley highlights the fact that the cost model does not include management of grade 2 or worse hypertension or other potential problems that may be caused by bevacizumab or the other chemotherapy drugs.  To the extent that additional costs are added to the model, the cost-effectiveness ratio generated by the researchers would worsen.

Second, Dr. Hensley explains that out of necessity, the researchers’ cost-effectiveness model used PFS data due to the unavailability of overall survival or quality adjusted overall survival data in connection with the three most recent bevacizumab phase III clinical trials. This model construct assumes that the 3.8 month improvement in PFS (as reported by the GOG 218 trial investigators)  provides an improvement in the patient’s experience. Dr. Hensley emphasizes that most ovarian cancer recurrences are identified while the patient is still asymptomatic, with the help of CA-125 blood testing and computed tomography imaging (i.e., CT scan).  Stated differently, it may not be correct to assume that remaining radiographically progression-free for an addtional 3.8 months would improve a patient’s quality of life.  If GOG 218 ultimately finds that PCB-B does not improve overall survival, then the drug’s cost-effectiveness will drift farther away from an acceptable level, says Hensley.

Third, Dr. Hensley points out that only when PFS associated with PCB-B use was hypothetically extended to 32.1 months (observed PFS in GOG 218 was 14.1 months) by the researchers did the incremental cost-effectiveness ratio approach $100,000 per progression-free year of life saved.  Hensley believes that the bevacizumab data accrued to date suggests that a 32.1 month PFS is unlikely. Notably, median PFS is only 24 months among lower-risk patients with optimally debulked stage III ovarian cancer treated with intraperitoneal-based platinum drug/taxane drug therapy.

Fourth, Dr. Hensley explains that it may be possible to achieve a better incremental cost-effectiveness ratio based upon preliminary data derived from the Gynaecologic Cancer Intergroup (GCIG) phase III randomized clinical trail of paclitaxel plus carboplatin, with or without bevacizumab and bevacizumab maintenace therapy (ICON7 trial). The bevacizumab dose tested in ICON7 was only half of that used in GOG 218 (7.5 mg/kg versus 15 mg/kg), and the duration of maintenance therapy in ICON7 was only 36 weeks of continued treatment as compared to 51 weeks in GOG 218. Preliminary results reported by the GCIG in ICON7 indicate that bevacizumab creates a PFS advantage in line with that produced in GOG 218, but at half the dose. Based on these facts, Hensley states that potential use of lower-dose and shorter-duration bevacizumab would improve the incremental cost-effectiveness ratio. Moreover, if lower dose/shorter duration bevacizumab use is also found to reduce the frequency of grade 2 or worse hypertension, the overall costs associated with the drug would also be lower, says Hensley.

Dr. Hensley believes that there are additional steps to be taken (and questions to be answered) which could improve an evaluation of the role and costs of bevacizumab:

  • Is there a clinically meaningful overall survival advantage to PCB-B over paclitaxel plus carboplatin? If PCB-B is not effective, then by definition, it is not cost-effective.
  • Is the data from ICON7 sufficient to permit treatment at half the dose for 9 months instead of 12 months? If so, total bevacizumab costs would be lower.
  • Is there a subset of patients who benefit dramatically from PCB-B?
  • If there is a subset of patients who benefit dramatically from PCB-B, it is necessary to study this group of women to determine if potential biomarkers can identify which patients will or will not benefit from the addition of bevacizumab. Identifying biomarkers that can predict response means commitment to correlative studies as part of large clinical trials.

In sum, Dr. Hensley believes that buying bevacizumab at $78.3 million for 3.8 months of progression-free survival on behalf of approximately 600 women is not sustainable in today’s health care delivery system. Moreover, the incurrence of such costs may hinder basic clinical research to find better compounds that improve PFS by a more meaningful magnitude, says Dr. Hensley.  From Hensley’s perspective, it appears that the stage is set for a potential collision between medicine and policy with respect to where and how a finite number of health care dollars will be spent.

About the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (cancer.osu.edu) is one of only 40 Comprehensive Cancer Centers in the United States designated by the National Cancer Institute. Ranked by U.S. News & World Report among the top cancer hospitals in the nation, The Arthur G. James Hospital is the 205-bed adult patient-care component of the cancer program at The Ohio State University. The OSUCCC – James is one of only seven funded programs in the country approved by the NCI to conduct both phase I and II clinical trials.

Sources:

2011 SGO Annual Meeting: Ovarian Cancer Abstracts Selected For Presentation

Posted on by

The March 2011 supplemental issue of Gynecologic Oncology sets forth the ovarian cancer and ovarian cancer-related medical abstracts selected by the Society of Gynecologic Oncologists for presentation at its 42nd Annual Meeting on Women’s Cancer™, which is being held in Orlando, Florida from March 6-9, 2011.

The Society of Gynecologic Oncologists (SGO) is hosting its 42nd Annual Meeting on Women’s Cancer™ (March 6–9, 2011) in Orlando, Florida. The SGO Annual Meeting attracts more than 1,700 gynecologic oncologists and other health professional from around the world.

In connection with this premier gynecologic cancer event, 651 abstracts, and 27 surgical films were submitted for consideration. After careful discussion and deliberation, the SGO selected 51 abstracts for oral presentation (27 Plenary session papers, 24 Focused Plenary papers, and 42 Featured Posters, presented in a new, electronic format), along with 227 for poster presentation. Of the 27 surgical films originally submitted, five films were selected for presentation during a featured Focused Plenary session.

The ovarian cancer abstracts listed below were obtained from the March 2011 supplemental issue of Gynecologic Oncology. Each abstract bears the number that it was assigned in the Gynecologic Oncology journal table of contents.

Please note that we provide below (under the heading “Additional Information”) Adobe Reader PDF copies of the 2011 SGO Annual Meeting program summary and the medical abstract booklet (includes all gynecologic cancer topics). If you require a free copy of the Adobe Reader software, please visit http://get.adobe.com/reader/otherversions/.

For your convenience, we listed the 2011 SGO Annual Meeting ovarian cancer abstracts under the following subject matter headings:  (1) ovarian cancer symptoms, (2) ovarian cancer screening, (3) pathology, (4) ovarian cancer staging, (5) chemotherapy, (6) diagnostic and prognostic biomarkers, (7) clinical trial drugs and results, (8) hereditary breast & ovarian cancer syndrome (BRCA gene deficiencies & Lynch Syndrome), (9) gynecologic practice, (10) gynecologic surgery, (11) genetic/molecular profiling, (12) immunotherapy, (13) medical imaging, (14) preclinical studies – general, (15) preclinical studies – potential therapeutic targets, (16) palliative and supportive care, (17) rare ovarian cancers, (18) survival data, (19) survivorship, (20) other, (21) late breaking abstracts.

Ovarian Cancer Symptoms

142. Utility of symptom index in women at increased risk for ovarian cancer. (SGO Abstract #140)

184. Symptom-triggered screening for ovarian cancer: A pilot study of feasibility and acceptability. (SGO Abstract #182)

187. Women without ovarian cancer reporting disease-specific symptoms. (SGO Abstract #185)

Ovarian Cancer Screening

12. Ovarian cancer: Predictors of primary care physicians’ referral to gynecologic oncologists. (SGO Abstract #10)

84. Long-term survival of patients with epithelial ovarian cancer detected by sonographic screening. (SGO Abstract #82)

90. Significant endometrial pathology detected during a transvaginal ultrasound screening trial for ovarian cancer. (SGO Abstract #88)

109. Detection of the tissue-derived biomarker peroxiredoxin 1 in serum of patients with ovarian cancer: A biomarker feasibility study. (SGO Abstract #107)

113. Epithelial ovarian cancer tumor microenvironment is a favorable biomarker resource. (SGO Abstract #111)

127. Stop and smell the volatile organic compounds: A novel breath-based bioassay for detection of ovarian cancer. (SGO Abstract #125)

144. Incidental gynecologic FDG-PET/CT findings in women with a history of breast cancer. (SGO Abstract #142)

156. Discovery of novel monoclonal antibodies (MC1–MC6) to detect ovarian cancer in serum and differentiate it from benign tumors. (SGO Abstract #154)

158. Evaluation of the risk of ovarian malignancy algorithm (ROMA) in women with a pelvic mass presenting to general gynecologists. (SGO Abstract #156)

162. Human epididymis protein 4 increases specificity for the detection of invasive epithelial ovarian cancer in premenopausal women presenting with an adnexal mass. (SGO Abstract #160)

163. Identification of biomarkers to improve specificity in preoperative assessment of ovarian tumor for risk of cancer. (SGO Abstract #161)

171. OVA1 has high sensitivity in identifying ovarian malignancy compared with preoperative assessment and CA-125. (SGO Abstract #169)

172. OVA1 improves the sensitivity of the ACOG referral guidelines for an ovarian mass. (SGO Abstract #170)

182. Sonographic predictors of ovarian malignancy. (SGO Abstract #180)

237. Management of complex pelvic masses using the OVA1 test: A decision analysis. (SGO Abstract #235)

241. Three-dimensional power doppler angiography as a three-step technique for differential diagnosis of adnexal masses: A prospective study. (SGO Abstract #239)

Pathology

145. Accuracy of frozen-section diagnosis of ovarian borderline tumor. (SGO Abstract #143)

Ovarian Cancer Staging

31. Should stage IIIC ovarian cancer be further stratified by intraperitoneal versus retroperitoneal-only disease? A Gynecologic Oncology Group study. (SGO Abstract #29)

173. Peritoneal staging biopsies in early-stage ovarian cancer: Are they necessary? (SGO Abstract #171)

Chemotherapy

29. Treatment of chemotherapy-induced anemia in patients with ovarian cancer: Does the use of erythropoiesis-stimulating agents worsen survival? (SGO Abstract #27)

69. Intraperitoneal chemotherapy for recurrent ovarian cancer appears efficacious with high completion rates and low complications. (SGO Abstract #67)

174. Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer. (SGO Abstract #172)

177. Sequencing of therapy and outcomes associated with use of neoadjuvant chemotherapy in advanced epithelial ovarian cancer in the Medicare population. (SGO Abstract #175)

179. Should we treat patients with ovarian cancer with positive retroperitoneal lymph nodes with intraperitoneal chemotherapy? Impact of lymph node status in women undergoing intraperitoneal chemotherapy. (SGO Abstract #177)

229. Predictors and effects of reduced relative dose intensity in women receiving their primary course of chemotherapy for ovarian cancer. (SGO Abstract #227)

Diagnostic & Prognostic Biomarkers

128. Stress and the metastatic switch in epithelial ovarian carcinoma. (SGO Abstract #126)

130. The cytoskeletal gateway for tumor aggressiveness in ovarian cancer is driven by class III β-tubulin. (SGO Abstract #128)

134. True blood: Platelets as a biomarker of ovarian cancer recurrence. (SGO Abstract #132)

148. CA-125 changes can predict optimal interval cytoreduction in patients with advanced-stage epithelial ovarian cancer treated with neoadjuvant chemotherapy. (SGO Abstract #146)

149. CA-125 surveillance for women with ovarian, fallopian tube or primary peritoneal cancers: What do survivors think? (SGO Abstract #147)

150. Calretinin as a prognostic indicator in granulosa cell tumor. (SGO Abstract #148)

135. Tumor expression of the type I insulin-like growth factor receptor is an independent prognostic factor in epithelial ovarian cancer. (SGO Abstract #133)

147. C-terminal binding protein 2: A potential marker for response to histone deacetylase inhibitors in epithelial ovarian cancer. (SGO Abstract #145)

157. Elevated serum adiponectin levels correlate with survival in epithelial ovarian cancers. (SGO Abstract #155)

175. Prognostic impact of prechemotherapy HE4 and CA-125 levels in patients with ovarian cancer. (SGO Abstract #175)

178. Serum HE4 level is an independent risk factor of surgical outcome and prognosis of epithelial ovarian cancer. (SGO Abstract #176)

Clinical Trial Drugs & Results

8. MicroRNA as a novel predictor of response to bevacizumab in recurrent serous ovarian cancer: An analysis of The Cancer Genome Atlas. (SGO Abstract #6)

9. Prospective investigation of risk factors for gastrointestinal adverse events in a phase III randomized trial of bevacizumab in first-line therapy of advanced epithelial ovarian cancer, primary peritoneal cancer or fallopian tube cancer: A Gynecologic Oncology Group study. (SGO Abstract #7)

10. First in human trial of the poly(ADP)-ribose polymerase inhibitor MK-4827 in patients with advanced cancer with antitumor activity in BRCA-deficient and sporadic ovarian cancers.  (SGO Abstract #8)

30. An economic analysis of intravenous carboplatin plus dose-dense weekly paclitaxel versus intravenous carboplatin plus every three-weeks paclitaxel in the upfront treatment of ovarian cancer. (SGO Abstract #28)

51. BRCA1-deficient tumors demonstrate enhanced cytotoxicity and T-cell recruitment following doxil treatment. (SGO Abstract #49)

54. A novel combination of a MEK inhibitor and fulvestrant shows synergistic antitumor activity in estrogen receptor-positive ovarian carcinoma. (SGO Abstract #52)

68. An economic analysis of bevacizumab in recurrent treatment of ovarian cancer. (SGO Abstract #66)

71. A phase II study of gemcitabine, carboplatin and bevacizumab for the treatment of platinum-sensitive recurrent ovarian cancer. (SGO Abstract #69)

72. A phase I clinical trial of a novel infectivity-enhanced suicide gene adenovirus with gene transfer imaging capacity in patients with recurrent gynecologic cancer. (SGO Abstract #70)

73. A phase I study of a novel lipopolymer-based interleukin-12 gene therapeutic in combination with chemotherapy for the treatment of platinum-sensitive recurrent ovarian cancer. (SGO Abstract #71)

74. AMG 386 combined with either pegylated liposomal doxorubicin or topotecan in patients with advanced ovarian cancer: Results from a phase Ib study. (SGO Abstract #72)

86. Pressure to respond: Hypertension predicts clinical benefit from bevacizumab in recurrent ovarian cancer. (SGO Abstract #84)

152. Changes in tumor blood flow as estimated by dynamic-contrast MRI may predict activity of single-agent bevacizumab in recurrent epithelial ovarian cancer and primary peritoneal cancer: An exploratory analysis of a Gynecologic Oncology Group phase II trial. (SGO Abstract #150)

153. Comparing overall survival in patients with epithelial ovarian, primary peritoneal or fallopian tube cancer who received chemotherapy alone versus neoadjuvant chemotherapy followed by delayed primary debulking. (SGO Abstract #151)

154. Consolidation paclitaxel is more cost-effective than bevacizumab following upfront treatment of advanced ovarian cancer. (SGO Abstract #152)

193. Pegylated liposomal doxorubicin with bevacizumab in the treatment of platinum-resistant ovarian cancer: Toxicity profile results. (SGO Abstract #191)

194. Phase II Trial of docetaxel and bevacizumab in recurrent ovarian cancer within 12 months of prior platinum-based chemotherapy. (SGO Abstract #192)

195. A phase I/II trial of IDD-6, an autologous dendritic cell vaccine for women with advanced ovarian cancer in remission. (SGO Abstract #193)

183. STAC: A phase II study of carboplatin/paclitaxel/bevacizumab followed by randomization to either bevacizumab alone or erlotinib and bevacizumab in the upfront management of patients with ovarian, fallopian tube or peritoneal cancer. (SGO Abstract #181)

228. Is it more cost-effective to use bevacizumab in the primary treatment setting or at recurrence? An economic analysis. (SGO Abstract #226)

240. The use of bevacizumab and cytotoxic and consolidation chemotherapy for the upfront treatment of advanced ovarian cancer: Practice patterns among medical and gynecologic oncology SGO members. (SGO Abstract #238)

Hereditary Breast & Ovarian Cancer Syndrome (BRCA gene deficiencies & Lynch Syndrome)

39. BRCAness profile of ovarian cancer predicts disease recurrence. (SGO Abstract #37)

52. A history of breast carcinoma predicts worse survival in BRCA1 and BRCA2 mutation carriers with ovarian carcinoma. (SGO Abstract #52)

137. Does genetic counseling for women at high risk of harboring a deleterious BRCA mutation alter risk-reduction strategies and cancer surveillance behaviors? (SGO Abstract #135)

138. Hereditary breast and ovarian cancer syndrome based on family history alone and implications for patients with serous carcinoma. (SGO Abstract #138)

139. Management and clinical outcomes of women with BRCA1/2 mutations found to have occult cancers at the time of risk-reducing salpingo-oophorectomy. (SGO Abstract #137)

141. The impact of BRCA testing on surgical treatment decisions for patients with breast cancer. (SGO Abstract #139)

136. Compliance with recommended genetic counseling for Lynch syndrome: Room for improvement. (SGO Abstract #134)

Gynecologic Practice

81. Availability of gynecologic oncologists for ovarian cancer care. (SGO Abstract #79)

Gynecologic Surgery

19. Single-port paraaortic lymph node dissection. (SGO Abstract #17)

20. Robotic nerve-sparing radical hysterectomy type C1. (SGO Abstract #18)

21. Urinary reconstruction after pelvic exenteration: Modified Indiana pouch. (SGO Abstract #19)

22. Intrathoracic cytoreductive surgery by video-assisted thoracic surgery in advanced ovarian carcinoma. (SGO Abstract #20)

26. Cost comparison of strategies for the management of venous thromboembolic event risk following laparotomy for ovarian cancer. (SGO Abstract #24)

28. Primary debulking surgery versus neoadjuvant chemotherapy in stage IV ovarian cancer. (SGO Abstract #26)

33. Does the bedside assistant matter in robotic surgery: An analysis of patient outcomes in gynecologic oncology. (SGO Abstract #31)

48. Defining the limits of radical cytoreductive surgery for ovarian cancer. (SGO Abstract #46)

87. Prognostic impact of lymphadenectomy in clinically early-stage ovarian malignant germ cell tumor. (SGO Abstract #85)

93. Secondary cytoreductive surgery: A key tool in the management of recurrent ovarian sex cord–stromal tumors. (SGO Abstract #91)

146. Advanced-stage ovarian cancer metastases to sigmoid colon mesenteric lymph nodes: Clinical consideration of tumor spread and biologic behavior. (SGO Abstract #144)

155. Cytoreductive surgery for serous ovarian cancer in patients 75 years and older. (SGO Abstract #153)

168. Intraperitoneal catheters placed at the time of bowel surgery: A review of complications. (SGO Abstract #166)

169. Laparoscopic versus laparotomic surgical staging for early-stage epithelial ovarian cancer. (SGO Abstract #167)

170. Oncologic and reproductive outcomes of cystectomy compared with oophorectomy as treatment for borderline ovarian tumor. (SGO Abstract #168)

180. Significance of perioperative infectious disease in patients with ovarian cancer. (SGO Abstract #178)

185. The feasibility of mediastinal lymphadenectomy in the management of advanced and recurrent ovarian carcinoma. (SGO Abstract #183)

235. Incidence of venous thromboembolism after robotic surgery for gynecologic malignancy: Is dual prophylaxis necessary? (SGO Abstract #233)

286. Charlson’s index: A validation study to predict surgical adverse events in gynecologic oncology. (SGO Abstract #284)

288. Cost-effectiveness of extended postoperative venous thromboembolism prophylaxis in gynecologic pncology patients. (SGO Abstract #286)

302. Integration of and training for robot-assisted surgery in a gynecologic oncology fellowship program. (SGO Abstract #300)

303. Outcomes of patients with gynecologic malignancies undergoing video-assisted thorascopic surgery and pleurodesis for malignant pleural effusion. (SGO Abstract #301)

304. Perioperative and pathologic outcomes following robot-assisted laparoscopic versus abdominal management of ovarian cancer. (SGO Abstract #302)

307. Predictive risk factors for prolonged hospitalizations after gynecologic laparoscopic surgery. (SGO Abstract #305)

309. Robot-assisted surgery for gynecologic cancer: A systematic review. (SGO Abstract #307)

310. Robotic radical hysterectomy: Extent of tumor resection and operative outcomes compared with laparoscopy and exploratory laparotomy. (SGO Abstract #308)

315. Utilization of specialized postoperative services in a comprehensive surgical cytoreduction program. (SGO Abstract #313)

Genetic/Molecular Profiling

5. A 3’ UTR KRAS variant as a biomarker of poor outcome and chemotherapy resistance in ovarian cancer. (SGO Abstract #3)

15. XPC single-nucleotide polymorphisms correlate with prolonged progression-free survival in advanced ovarian cancer. (SGO Abstract #13)

16. Genomewide methylation analyses reveal a prominent role of HINF1 network genes, via hypomethylation, in ovarian clear cell carcinoma. (SGO Abstract #14)

49. Loss of ARID1A is a frequent event in clear cell and endometrioid ovarian cancers. (SGO Abstract #47)

53. Genetic variants in the mammalian target of rapamycin (mTOR) signaling pathway as predictors of clinical response and survival in women with ovarian cancer. (SGO Abstract #51)

55. BAD apoptosis pathway expression and survival from cancer. (SGO Abstract #53)

59. Molecular profiling of advanced pelvic serous carcinoma associated with serous tubal intraepithelial carcinoma. (SGO Abstract #57)

82. Biologic roles of tumor and endothelial delta-like ligand 4 in ovarian cancer. (SGO Abstract #80)

85. MicroRNA 101 inhibits ovarian cancer xenografts by relieving the chromatin-mediated transcriptional repression of p21waf1/cip1. (SGO Abstract #83)

102. Association between global DNA hypomethylation in leukocytes and risk of ovarian cancer. (SGO Abstract #100)

103. Cisplatin, carboplatin, and paclitaxel: Unique and common pathways that underlie ovarian cancer response. (SGO Abstract #101)

106. Comparison of mTOR and HIF pathway alterations in the clear cell carcinoma variant of kidney, ovary and endometrium. (SGO Abstract #104)

107. Concordant gene expression profiles in matched primary and recurrent serous ovarian cancers predict platinum response. (SGO Abstract #105)

111. Differential microRNA expression in cis-platinum-resistant versus -sensitive ovarian cancer cell lines. (SGO Abstract #109)

112. DNA methylation markers associated with serous ovarian cancer subtypes. (SGO Abstract #110)

118. MicroRNA and messenger RNA pathways associated with ovarian cancer cell sensitivity to topotecan, gemcitabine and doxorubicin. (SGO Abstract #116)

119. Molecular profiling of patients with curatively treated advanced serous ovarian carcinoma from The Cancer Genome Atlas. (SGO Abstract #117)

125. Proteomic analysis demonstrates that BRCA1-deficient epithelial ovarian cancer cell lines activate alternative pathways following exposure to cisplatin. (SGO Abstract #123)

132. The tumor suppressor KLF6, lost in a majority of ovarian cancer cases, represses VEGF expression levels. (SGO Abstract #130)

126. Quantitative PCR array identification of microRNA clusters associated with epithelial ovarian cancer chemoresistance. (SGO Abstract #124)

160. Genes functionally regulated by methylation in ovarian cancer are involved in cell proliferation, development and morphogenesis. (SGO Abstract #158)

181. Single-nucleotide polymorphism in DNA repair and drug resistance genes alone or in combination in epithelail ovarian cancer. (SGO Abstract #179)

278. Expression patterns of p53 and p21 cell cycle regulators and clinical outcome in women with pure gynecologic sarcomas. (SGO Abstract #276)

Immunotherapy

98. Ab-IL2 fusion proteins mediate NK cell immune synapse formation in epithelial ovarian cancer by polarizing CD25 to the target cell–effector cell interface. (SGO Abstract #96)

124. Proteasome inhibition increases death receptors and decreases major histocompatibility complex I expression: Pathways to exploit in natural killer cell immunotherapy. (SGO Abstract #122)

Medical Imaging

164. Impact of FDG-PET in suspected recurrent ovarian cancer and optimization of patient selection for cytoreductive surgery. (SGO Abstract #162)

294. The clinical and financial implications of MRI of pelvic masses. (SGO Abstract #292)

Preclinical Studies

11. A unique microRNA locus at 19q13.41 sensitizes epithelial ovarian cancers to chemotherapy. (SGO Abstract #9)

14. Common single-nucleotide polymorphisms in the BNC2, HOXD1 and MERIT40 regions contribute significantly to racial differences in ovarian cancer incidence. (SGO Abstract #12)

46. Development of a preclinical serous ovarian cancer mouse model. (SGO Abstract #44)

56. Examination of matched primary and recurrent ovarian cancer specimens supports the cancer stem cell hypothesis. (SGO Abstract #54)

58. Modeling of early events in serous carcinogenesis: Molecular prerequisites for transformation of fallopian tube epithelial cells. (SGO Abstract #56)

101. Antiproliferative activity of a phenolic extract from a native Chilean Amaranthaceae plant in drug-resistant ovarian cancer cell lines. (SGO Abstract #99)

115. Identification and characterization of CD44+/CD24–ovarian cancer stem cell properties and their correlation with survival. (SGO Abstract #113)

Preclinical Studies – Potential Therapeutic Targets

57. Hypoxia-mediated activation of signal transducer and activator of transcription 3 (STAT3) in ovarian cancer: A novel therapeutic strategy using HO-3867, a STAT3 inhibitor (and novel curcumin analog). (SGO Abstract #55)

61. The ubiquitin ligase EDD mediates platinum resistance and is a target for therapy in epithelial ovarian cancer. (SGO Abstract #59)

97. A novel hedgehog pathway smoothened inhibitor (BMS-833923) demonstrates in vitro synergy with carboplatin in ovarian cancer cells. (SGO Abstract #95)

100. AMPK activation mimics glucose deprivation and induces cytotoxicity in ovarian cancer cells. (SGO Abstract #98)

104. Clinical significance of vascular cell adhesion molecule 1 (VCAM-1) in the ovarian cancer microenvironment. (SGO Abstract #102)

105. Combined erbB/VEGFR blockade has improved anticancer activity over single-pathway inhibition in ovarian cancer in vivo. (SGO Abstract #103)

114. EZH2 expression correlates with increased angiogenesis in ovarian carcinoma. (SGO Abstract #112)

116. Induction of apoptosis in cisplatin-resistant ovarian cancer cells by G-1, a specific agonist of the G-protein-coupled estrogen receptor GPR30. (SGO Abstract #114)

120. Neuropilin-1 blockade in the tumor microenvironment reduces tumor growth. (SGO Abstract #118)

129. Targeting the hedgehog pathway reverses taxane resistance in ovarian cancer. (SGO Abstract #127)

121. Ovarian cancer lymph node metastases express unique cellular structure and adhesion genes. (SGO Abstract #119)

122. Overexpression of fibroblast growth factor 1 and fibroblast growth factor receptor 4 in high-grade serous ovarian carcinoma: Correlation with survival and implications for therapeutic targeting. (SGO Abstract #120)

131. The pattern of H3K56 acetylation expression in ovarian cancer. (SGO Abstract #129)

133. Thinking outside of the tumor: Targeting the ovarian cancer microenvironment. (SGO Abstract #131)

161. Horm-A domain-containing protein 1 (HORMAD1) and outcomes in patients with ovarian cancer. (SGO Abstract #159)

165. Influence of the novel histone deacetylase inhibitor panobinostat (LBH589) on the growth of ovarian cancer. (SGO Abstract #163)

166. Inhibition of stress-induced phosphoprotein 1 decreases proliferation of ovarian cancer cell lines. (SGO Abstract #164)

167. Insulin-like growth factor receptor 1 pathway signature correlates with adverse clinical outcome in ovarian cancer. (SGO Abstract #165)

230. Therapeutic synergy and resensitization of drug-resistant ovarian carcinoma to cisplatin by HO-3867. (SGO Abstract #228)

Palliative & Supportive Care

159. Factors associated with hospice use in ovarian cancer. (SGO Abstract #226)

190. Age-related preferences regarding end-of-life care discussions among gynecologic oncology patients. (SGO Abstract #188)

192. Palliative care education in gynecologic oncology: A survey of the fellows. (SGO Abstract #190)

Rare Ovarian Cancers

151. Carcinosarcoma of the ovary: A case–control study. (SGO Abstract #149)

Survival Data

80. Ten-year relative survival for epithelial ovarian cancer. (SGO Abstract #78)

83. Impact of beta blockers on epithelial ovarian cancer survival. (SGO Abstract #81)

176. Revisiting the issue of race-related outcomes in patients with stage IIIC papillary serous ovarian cancer who receive similar treatment. (SGO Abstract #174)

186. The impact of diabetes on survival in women with ovarian cancer. (SGO Abstract #184)

284. Survival following ovarian versus uterine carcinosarcoma. (SGO Abstract #282)

285. The unique natural history of mucinous tumors of the ovary. (SGO Abstract #283)

292. Stage IC ovarian cancer: Tumor rupture versus ovarian surface involvement. (SGO Abstract #290)

Survivorship

191. Menopausal symptoms and use of hormone replacement therapy: The gynecologic cancer survivors’ perspective. (SGO Abstract #189)

Other

4. From guidelines to the front line: Only a minority of the Medicare population with advanced epithelial ovarian cancer receive optimal therapy. (SGO Abstract #2)

32. Efficacy of influenza vaccination in women with ovarian cancer. (SGO Abstract #30)

91. Women with invasive gynecologic malignancies are more than 12 times as likely to commit suicide as are women in the general population. (SGO Abstract #89)

231. Attrition of first-time faculty in gynecologic oncology: Is there a difference between men and women? (SGO Abstract #229)

238. Relative impact of cost drivers on the increasing expense of inpatient gynecologic oncology care. (SGO Abstract #236)

Late-Breaking Abstracts

About Society of Gynecologic Oncologists (SGO)

The SGO is a national medical specialty organization of physicians and allied healthcare professionals who are trained in the comprehensive management of women with malignancies of the reproductive tract. Its purpose is to improve the care of women with gynecologic cancer by encouraging research, disseminating knowledge which will raise the standards of practice in the prevention and treatment of gynecologic malignancies, and cooperating with other organizations interested in women’s health care, oncology and related fields. The Society’s membership, totaling more than 1,400, is primarily comprised of gynecologic oncologists, as well as other related medical specialists including medical oncologists, radiation oncologists, nurses, social workers and pathologists. SGO members provide multidisciplinary cancer treatment including chemotherapy, radiation therapy, surgery and supportive care. More information on the SGO can be found at www.sgo.org.

About Gynecologic Oncologists

Gynecologic oncologists are physicians committed to the comprehensive treatment of women with cancer. After completing four years of medical school and four years of residency in obstetrics and gynecology, these physicians pursue an additional three to four years of training in gynecologic oncology through a rigorous fellowship program overseen by the American Board of Obstetrics and Gynecology. Gynecologic oncologists are not only trained to be skilled surgeons capable of performing wide-ranging cancer operations, but they are also trained in prescribing the appropriate chemotherapy for those conditions and/or radiation therapy when indicated. Frequently, gynecologic oncologists are involved in research studies and clinical trials that are aimed at finding more effective and less toxic treatments to further advance the field and improve cure rates.

Studies on outcomes from gynecologic cancers demonstrate that women treated by a gynecologic oncologist have a better likelihood of prolonged survival compared to care rendered by non-specialists. Due to their extensive training and expertise, gynecologic oncologists often serve as the “team captain” who coordinates all aspects of a woman’s cancer care and recovery. Gynecologic oncologists understand the impact of cancer and its treatments on all aspects of women’s lives including future childbearing, sexuality, physical and emotional well-being—and the impact cancer can have on the patient’s whole family.

Sources:

Additional Information:


York University Researchers Identify Genetic Process That May Underlie Ovarian Cancer Chemoresistance

Posted on by

York University researchers have identified a genetic process that may allow ovarian cancer to resist chemotherapy.

York University researchers have zeroed in on a genetic process that may allow ovarian cancer to resist chemotherapy.

Researchers in the York University Faculty of Science & Engineering studied a tiny strand of our genetic makeup known as a microRNA (miRNA), involved in the regulation of gene expression. Cancer occurs when gene regulation goes haywire.

For many years, DNA and proteins have been viewed as the real movers and shakers in genomic studies, with RNA seen as little more than a messenger that shuttles information between the two. In fact, miRNA was considered relatively unimportant less than a decade ago; that is no longer the case. MiRNA seems to stifle the production of proteins exclusively — a function opposite that of its better-known relative, messenger RNA, or mRNA, which translates instructions from genes to create proteins.  MiRNA attaches to a piece of mRNA – which is the master template for building a protein, thereby acting as a signal to prevent translation of the mRNA into a protein. The “silencing” of proteins by miRNAs can be a good or a bad thing, depending on the circumstances.

Chun Peng, Ph.D., Professor of Biology, York University, and her team identified a genetic process involving a "microRNA" that may underlie a form of ovarian cancer chemoresistance.

“Ovarian cancer is a very deadly disease because it’s hard to detect,” says biology professor Chun Peng, who co-authored the study. “By the time it’s diagnosed, usually it is in its late stages. And by that point there’s really no way to treat the disease.” “Even when the disease is discovered in its early stages, chemotherapy doesn’t always work,” she says.

Peng was among a team of researchers that discovered a receptor, ALK7 (activin receptor-like kinase 7), that induces cell-death in epithelial ovarian cancer cells.[1] They have now discerned that miRNA 376c targets this crucial receptor, inhibiting its expression and allowing ovarian cancer cells to thrive.[2]

“Our evidence suggests that miRNA 376c is crucial to determining how a patient will respond to a chemotherapeutic agent,” says Peng. “It allows cancer cells to survive by targeting the very process that kills them off,” she says.

In examining tumors taken from patients who were non-responsive to chemotherapy, researchers found a higher expression of miRNA 376c and a much lower expression of ALK7.  Peng believes that this research is a step towards being able to make chemotherapy drugs more effective in the treatment of the disease.

“Further study is needed, but ultimately if we can introduce anti-microRNAs that would lower the level of those microRNAs that make cancer cells resistant to chemotherapeutic drugs, we will be able to make chemotherapy more effective against ovarian cancer,” Peng says.

She urges women to educate themselves about the risk factors and symptoms of the disease. For more information, visit http://www.ovariancanada.org.

Peng is a world expert in the area of ovarian cancer and the molecular basis of complications in pregnancy. Her research on chemoresistance has also contributed to knowledge and prediction of pre-eclampsia, a pregnancy disorder that is a leading cause of maternal and perinatal complications and death.

The article, MicroRNA 376c enhances ovarian cancer cell survival by targeting activin receptor-like kinase 7: implications for chemoresistance, was published in the Journal of Cell Science.[2]

The study’s lead author, Gang Ye, is a Research Associate in Peng’s lab. Several trainees in Peng’s lab, as well as scientists in Toronto’s Sunnybrook Research Institute and in China, also participated in the project.

The research was supported by an operating grant from the Canadian Institutes of Health Research (CIHR) and a mid-career award to Peng from the Ontario Women’s Health Council/CIHR. Ye was supported in part by a Fellowship from the Toronto Ovarian Cancer Research Network.

About York University

York University is the leading interdisciplinary research and teaching university in Canada. York offers a modern, academic experience at the undergraduate and graduate level in Toronto, Canada’s most international city. The third largest university in the country, York is host to a dynamic academic community of 50,000 students and 7,000 faculty and staff, as well as 200,000 alumni worldwide. York’s 10 Faculties and 28 research centres conduct ambitious, groundbreaking research that is interdisciplinary, cutting across traditional academic boundaries. This distinctive and collaborative approach is preparing students for the future and bringing fresh insights and solutions to real-world challenges. York University is an autonomous, not-for-profit corporation.

References:

1/Xu G, Zhou H, Wang Q, et. al. Activin receptor-like kinase 7 induces apoptosis through up-regulation of Bax and down-regulation of Xiap in normal and malignant ovarian epithelial cell lines. Mol Cancer Res. 2006 Apr;4(4):235-46. PubMed PMID: 16603637.

2/Ye G, Fu G, Cui S, et. al. MicroRNA 376c enhances ovarian cancer cell survival by targeting activin receptor-like kinase 7: implications for chemoresistance. J Cell Sci. 2011 Feb 1;124(Pt 3):359-68. Epub 2011 Jan 11. PubMed PMID: 21224400.

Source: York U researchers uncovering how ovarian cancer resists chemotherapy, Press Release, York University, March 2, 2011.


Mrs. Australia Quest Finalist Veronica Cristovao Is Raising Ovarian Cancer Awareness “Down Under”

Posted on by

Mrs. Australian Quest Finalist Veronica Cristovao is raising ovarian cancer awareness “Down Under,” and she hopes to use the pageant as an international platform to further her ovarian cancer advocacy.

Did you know that February is national Ovarian Cancer Awareness Month in Australia?

Veronica Cristovao is a finalist in the Mrs. Australia Quest pageant which supports Ovarian Cancer Australia. Veronica hopes to use the pageant as an international platform for ovarian cancer awareness.

According to the Australian National Breast and Ovarian Cancer Centre, approximately 1,200 Australian women were diagnosed with ovarian cancer in 2010.  On average, three Australian women are diagnosed with ovarian cancer every day, while two Australian women die from the disease every day or one woman every twelve hours.  Ovarian cancer accounts for 55 percent of all Australian gynecological cancer deaths. By way of comparison, 88 out of every 100 Australian women diagnosed with breast cancer will be alive five years after diagnosis, whereas only 40 out of every 100 Australian women diagnosed with ovarian cancer will be alive during that same time period.

These statistics are alarming, and until effective prevention and early detection methods can be identified, awareness of the ovarian cancer early warning signs are critical. Promotion of ovarian cancer awareness and early detection underlie the charitable mission of the Mrs. Australia Quest pageant. The pageant’s mission is artfully expressed through its “beautiful awareness” motto.

Although February has come to an end, we had the pleasure of getting to know Veronica Cristovao, a Mrs. Australia Quest Finalist, earlier this month.  Because the Mrs. Australia Quest pageant supports ovarian cancer awareness through Ovarian Cancer Australia, we thought it was important to highlight Veronica’s ovarian cancer advocacy and participation in the pageant.  After reading Veronica’s story, you will discover what we already know; win, lose or draw in the final pageant competition, Veronica is already a winner given her amazing talents as an entrepreneur, ovarian cancer advocate, wife, and mother of two young children.

We would like to extend our fullest appreciation to Veronica and her family for allowing us to tell her ovarian cancer advocacy story.

“Character contributes to beauty. It fortifies a woman as her youth fades. A mode of conduct, a standard of courage, discipline, fortitude, and integrity can do a great deal to make a woman beautiful.”

— Jacqueline Bisset, English Actress & Golden Globe and Emmy Award Nominee

Mrs. Australia Quest Pageant

The Mrs. Australia Quest pageant selected Ovarian Cancer Australia as its designated 2011 charity. Ovarian Cancer Australia was founded by individuals directly affected by ovarian cancer, who wanted to raise awareness of the disease and support those who have been affected by it. This founder group includes:

  • Nicole Livingstone, a retired Australian swimmer and Olympic medal winner, television sports commentator and radio presenter, and recipient of the Order of Australia Metal, and her sister Karen, who lost their mother and aunt to the disease;
  • Simon Lee, whose wife Sheila was the driving force behind the Australian ovarian cancer awareness movement prior to her death in 2001;
  • Actress and comedian Lynda Gibson, who was diagnosed with ovarian cancer in 2000 and subsequently lost her battle to the disease in 2004; and
  • Journalist Tracey Curro, whose mother died from ovarian cancer.

Ovarian Cancer Australia is the country’s only national not-for-profit organization which (i) supports women with ovarian cancer, their families, friends and caretakers with compassionate support programs and practical resources; (ii) educates communities and individuals about the disease to increase their awareness of symptoms and the latest treatment, research and clinical trials from across Australia; and (iii) advocates to improve outcomes, treatment and quality of life for women with ovarian cancer.  In 2011, Ovarian Cancer Australia will be celebrating its 10th anniversary.

In support of Ovarian Cancer Australia, the Mrs. Australia Quest pageant is promoting awareness of the early signs and symptoms of ovarian cancer in an attempt to educate the women of Australia and beyond. The overarching goal is to save as many women’s lives as possible.

All Mrs. Australia Quest pageant entrants receive the opportunity to promote themselves, voice their opinions, get involved, network, fulfill personal goals, and most of all to have fun. Moreover, the experience at the Mrs. Australia Quest National Final, which will be held in Sydney during June 2011, promises to be very glamorous and entertaining for all of the women who participate. All participants will be judged based upon the following criteria:  personal interview & Q&A submission, photographic session, Evening Attire Competition, Swimwear Competition, Active Wear Competition, promotion of ovarian cancer awareness, and internet popularity voting.  Undoubtedly, the Mrs. Australia Quest National Final title winner will experience a life changing event that will open new doors of opportunity and create memorable moments.

The Mrs. Australia Quest national winner will go on to compete in the Mrs. International® pageant which will be held in Chicago, Illinois during July 2011. In this pageant, each contestant has the opportunity to select a platform of her choice, which she will spend the next year promoting. Husbands also play a direct role in this event.  Each husband will escort his wife in the Evening Gown competition, and the Mrs. International® pageant winner’s husband will crown his wife as the new titleholder.

Veronica Cristovao – Mrs. Australia Quest Finalist

The Mrs. Australia Quest pageant not only raises money for ovarian cancer, it also raises the profile of the disease by creating ambassadors of young wives in Australia. The pageant’s charitable ovarian cancer awareness mission is what motivated Veronica Cristovao to take part in the 2011 competition.

The Cristovao family celebrates Thomas' 3rd birthday. (Above: Duarte & Veronica Cristovao with their two children; Thomas, a 3-year old boy, and Samantha, an 18-month old girl)

Veronica is 33 years old and is married to her husband Duarte, who is property developer.  The couple has two children; Thomas, a 3-year old boy, and Samantha, an 18-month old girl.

After experiencing the effects of cancer so close to home, Veronica knows all too well the importance of awareness. Veronica’s family relatives have been affected by cancer of the stomach and the breast, as well as lymphoma.

Veronica completed her formal education with a major in Business/Marketing and Computer Science, although she started her work career in the areas of customer service, management and training.  Despite that fact, her life-long passion has always been real estate. In fact, before having children, Veronica worked as a real estate agent.  She also engaged in part-time modeling and commercials, and met many interesting people along the way.

While pregnant with her first child (Thomas), Veronica studied interior design and decoration. Given her husband’s real estate development expertise, Veronica believed that a background in interior design and decoration would allow her to work side-by-side with Duarte, thereby allowing the couple to share a common passion. Veronica has already completed four major interior design/decoration projects, while raising her young children at the same time.  And, her business and marketing background has proved quite helpful in recruiting new clients for her rapidly growing business, which include her brother who happens to be an architect.

Veronica has always been engaged in charitable activities throughout her life, including blood donation and volunteer activities in support of local charitable organizations and children in need.  While working and raising a family, Veronica has also been active in raising ovarian cancer awareness. She dedicates a great deal of time to distributing ovarian cancer awareness posters and informational pamphlets within her local community.  By all accounts, Veronica’s ovarian cancer awareness campaign has been extremely well received by her community.

This past month, Veronica utilized an Ovarian Cancer Australia awareness campaign called, “Afternoon Teal™.” Through this campaign, Ovarian Cancer Australia invites all Australians to support women diagnosed with ovarian cancer and their families by hosting an Afternoon Teal™ during the month of February.  This gathering allows a host, such as Veronica, to invite workmates, friends, and family members to the event with the goal of (i) raising funds to support programs for women touched by ovarian cancer and their families; and (ii) providing vital information regarding the early warning signs and symptoms of ovarian cancer. Veronica hosted several successful Afternoon Teal™ events, thereby raising much needed monies for ovarian cancer awareness.

“Beauty is how you feel inside, and it reflects in your eyes. It is not something physical.”

— Sophia Loren, Italian Film Actress & 1962 “Best Actress” Academy Award (Oscar) Winner

During a recent interview with a local Australian news reporter, Veronica said:  “Cancer is a horrible disease. I feel so fortunate that I am happy and healthy, I want to take this opportunity to give something back.” Veronica believes that learning to “give back” is a critical life lesson for her children, which is best taught by example. “I want my children to understand how important it is to help people in need. I want them to know just how lucky we are.”

In the Mrs. Australia Quest pageant final to be held in June, Veronica will compete with seven other wives for the opportunity to represent Australia at an international level. Veronica believes that winning the national title in June will give her the requisite international platform to raise awareness about the devastating effects of ovarian cancer. Veronica would also like to note that ovarian cancer is preventable through various means, but as with any cancer, recognizing the early warning signs and symptoms is vital. Because there is no reliable blood test to detect early stage ovarian cancer, Veronica looks forward to the day when such a test is readily available at all Australian medical centers.

As noted above, Veronica has already taken it upon herself to campaign hard for ovarian cancer awareness. That hard work has already resulted in her receipt of approximately 7,500 online votes, which represent 10 percent of the final judging score to determine the next Mrs. Australia Quest.  We should note that 50% of monies raised through online voting support Ovarian Cancer Australia.

If you would like to vote for Veronica online, please visit http://www.mrsaustraliaquest.com.au/ and click on the “View Finalists” tab, which is located on the left margin of the Mrs. Australia Quest homepage. All individual donors who vote $100 (AUD) or more will be acknowledged on the Mrs. Australia Quest website. Three business voting packages are also available, which provide an even higher level of donor acknowledgment.

We would like to thank the Cristovao family again for helping us in the preparation of this story, and we wish Veronica all the best with respect to the Mrs. Australia Quest pageant final competition in June 2011. In our humble opinion, Veronica is already a winner and an inspirational ovarian cancer advocate.

Sources:

_________________________________________

*“Vox Populi,” a Latin phrase that means “voice of the people,” is a term often used in broadcast journalism to describe an interview of the “man (or woman) on the street.”

In the spirit of Vox Populi, Libby’s H*O*P*E*™ searches online for original writings and visual media created by ovarian cancer survivors, survivors’ family members, cancer advocates, journalists, and health care professionals, which address one or more aspects of ovarian cancer within the context of daily life. The written and visual media features that we discover run the gamut; sometimes poignant, sometimes educational, sometimes touching, sometimes comedic, but always honest. The Vox Populi feature may take the form of an essay, editorial, poem, letter, story, song or video picture montage.

It is our hope that the Vox Populi feature will allow our readers to obtain, in some small way, a better understanding of how ovarian cancer impacts the life of a woman diagnosed with the disease and her family. We invite all readers to submit, or bring to our attention, original writings and visual media suitable for publication as Vox Populi features.