Yale University Scientists Synthesize Long-Sought-After Anticancer Agent

A team of Yale University scientists has synthesized for the first time a chemical compound  called “lomaiviticin aglycon, ” which led to the development of a new class of molecules that appear to target and destroy cancer stem cells.

A team of Yale University scientists has synthesized for the first time a chemical compound called “lomaiviticin aglycon,” which led to the development of a new class of molecules that appear to target and destroy cancer stem cells.

Chemists worldwide have been interested in lomaiviticin’s potential anticancer properties since its discovery in 2001. But so far, they have been unable to obtain significant quantities of the compound, which is produced by a rare marine bacterium that cannot be easily coaxed into creating the molecule. For the past decade, different groups around the world have been trying instead to synthesize the natural compound in the lab, but without success.

Dr. Seth Herzon (center), along with team members Christina Woo and Liang Lu, synthesized a naturally occurring anticancer compound that scientists worldwide have been trying to replicate in the lab for nearly a decade.

Now a team at Yale, led by chemist Dr. Seth Herzon, has managed to create lomaiviticin aglycon for the first time, opening up new avenues of exploration into novel chemotherapies that could target cancer stem cells, thought to be the precursors to tumors in a number of different cancers including ovarian, brain, lung, prostate and leukemia. Their discovery appears online today in the Journal of the American Chemical Society.

“About three quarters of anticancer agents are derived from natural products, so there’s been lots of work in this area,” Herzon said. “But this compound is structurally very different from other natural products, which made it extremely difficult to synthesize in the lab.”

In addition to lomaiviticin aglycon, Herzon’s team also created smaller, similar molecules that have proven extremely effective in killing ovarian stem cells, said Gil Mor, M.D., Ph.D., a researcher at the Yale School of Medicine who is collaborating with Herzon to test the new class of molecules’ potential as a cancer therapeutic. This family of compounds are called “kinamycins.” The reactive core of the kinamycins also plays a key role in lomaiviticin aglycon, which is even more toxic and could prove even more effective in destroying cancer cells.

The scientists are particularly excited about lomaiviticin aglycon’s potential to kill ovarian cancer stem cells because the disease is notoriously resistant to paclitaxel (Taxol) and carboplatin, two of the most commonly used ovarian cancer chemotherapy drugs. “Ovarian cancer has a high rate of recurrence, and after using chemotherapy to fight the tumor the first time, you’re left with resistant tumor cells that tend to keep coming back,” Mor explained. “If you can kill the stem cells before they have the chance to form a tumor, the patient will have a much better chance of survival — and there aren’t many potential therapies out there that target cancer stem cells right now.”

Image of one of the kinamycin compounds synthesized by Yale researchers destroying ovarian cancer cells (the spherical objects) in less than 48 hours in lab tests. (Credit: Gil Mor)

Herzon’s team, which managed to synthesize the molecule in just 11 steps starting from basic chemical building blocks, has been working on the problem since 2008 and spent more than a year on just one step of the process involving the creation of a carbon-carbon bond. It was an achievement that many researchers deemed impossible, but while others tried to work around having to create that bond by using other techniques, the team’s persistence paid off.

“A lot of blood, sweat and tears went into creating that bond,” Herzon said. “After that, the rest of the process was relatively easy.”

Next, the team will continue to analyze the compound to better understand what’s happening to the stem cells at the molecular level. The team hopes to begin testing the compounds in animals shortly.

“This is a great example of the synergy between basic chemistry and the applied sciences,” Herzon said. “Our original goal of synthesizing this natural product has led us into entirely new directions that could have broad impacts in human medicine.”

Other authors of the paper include Liang Lu, Christina M. Woo and Shivajirao L. Gholap, all of Yale University.

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Outside-the-Body Filtration Device May Reduce Ovarian Cancer Cells In Abdominal Fluid

A paper published in the January issue of the journal Nanomedicine could provide the foundation for a new ovarian cancer treatment option — one that would use an outside-the-body filtration device to remove a large portion of the free-floating cancer cells that often create secondary tumors.

Schematic shows how fluids containing ovarian cancer cells could be removed from the body, treated with magnetic nanoparticles to remove the cells, then returned to the body. (Courtesy of Ken Scarberry)

Magnetic nanoparticles suspended in a liquid are attracted to a magnet. The nanoparticles could be attached to cancer cells and then removed from the body with magnetic filtration. (Credit: Gary Meek)

A paper published in the January issue of the journal Nanomedicine could provide the foundation for a new ovarian cancer treatment option — one that would use an outside-the-body filtration device to remove a large portion of the free-floating cancer cells that often create secondary tumors.

Researchers at the Georgia Institute of Technology have formed a startup company and are working with a medical device firm to design a prototype treatment system that would use magnetic nanoparticles engineered to capture cancer cells. Added to fluids removed from a patient’s abdomen, the magnetic nanoparticles would latch onto the free-floating cancer cells, allowing both the nanoparticles and cancer cells to be removed by magnetic filters before the fluids are returned to the patient’s body.

In mice with free-floating ovarian cancer cells, a single treatment with an early prototype of the nanoparticle-magnetic filtration system captured enough of the cancer cells that the treated mice lived nearly a third longer than untreated ones. The researchers expect multiple treatments to extend the longevity benefit, though additional research will be needed to document that — and determine the best treatment options.

“Almost no one dies from primary ovarian cancer,” said Dr. John McDonald, a professor in Georgia Tech’s School of Biology and chief research scientist of Atlanta’s Ovarian Cancer Institute. “You can remove the primary cancer, but the problem is metastasis. A good deal of the metastasis in ovarian cancer comes from cancer cells sloughing off into the abdominal cavity and spreading the disease that way.”

The removal system being developed by McDonald and postdoctoral fellow Ken Scarberry — who is also CEO of startup company Sub-Micro — should slow tumor progression in humans. It may reduce the number of free-floating cancer cells enough that other treatments, and the body’s own immune system, could keep the disease under control.

Professor John McDonald (standing) and postdoctoral fellow Ken Scarberry examine statistical data from their study of a potential new treatment option for ovarian cancer. (Credit: Gary Meek)

“If you can reduce metastasis, you can improve the lifespan of the person with the disease and get a better chance of treating it effectively,” said McDonald. “One goal is to make cancer a chronic disease that can be effectively treated over an extended period of time. If we can’t cure it, perhaps we can help people to live with it.”

Earlier in vitro studies published by the authors of the Nanomedicine paper showed that the magnetic nanoparticles could selectively remove human ovarian cancer cells from ascites fluid, which builds up in the peritoneal cavities of ovarian cancer patients. The nanoparticles are engineered with ligands that allow them to selectively attach to cancer cells.

The researchers believe that treating fluid removed from the body avoids potential toxicity problems that could result from introducing the nanoparticles into the body, though further studies are needed to confirm that the treatment would have no adverse effects.

The recently reported study in Nanomedicine used three sets of female mice to study the benefit of the nanoparticle-magnetic filtration system. Each mouse was injected with approximately 500,000 murine ovarian cancer cells, which multiply rapidly — each cell doubling within approximately 15 hours.

In the experimental group, the researchers — who included research scientist Roman Mezencev — removed fluid from the abdomens of the mice immediately after injection of the cancer cells. They then added the magnetic nanoparticles to the fluid, allowed them to mix, then magnetically removed the nanoparticles along with the attached cancer cells before returning the fluid. The steps were repeated six times for each mouse.

One control group received no treatment at all, while a second control group underwent the same treatment as the experimental group — but without the magnetic nanoparticles. Mice in the two control groups survived a median of 37 days, while the treated mice lived 12 days longer — a 32 percent increase in longevity.

Though much more research must be done before the technique can be tested in humans, McDonald and Scarberry envision a system very similar to what kidney dialysis patients now use, but with a buffer solution circulated through the peritoneal cavity to pick up the cancer cells.

“What we are developing is akin to hemofiltration or peritoneal dialysis in which the patient could come into a clinic and be hooked up to the device a couple of times a week,” said Scarberry. “The treatment is not heavily invasive, so it could be repeated often.”

The new treatment could be used in conjunction with existing chemotherapy and radiation. Reducing the number of free-floating cancer cells could allow a reduction in chemotherapy, which often has debilitating side effects, Scarberry said. The new treatment system could be used to capture spilled cancer cells immediately after surgery on a primary tumor.

The researchers hope to have a prototype circulation and filtration device ready for testing within three years. After that will come studies into the best treatment regimen, examining such issues as the number of magnetic nanoparticles to use, the number of treatments and treatment spacing. If those are successful, the company will work with the FDA to design human clinical trials.

The researchers also studying how their magnetic nanoparticles could be engineered to capture ovarian cancer stem cells, which are not affected by existing chemotherapy. Removing those cells could help eliminate a potent source of new cancer cells.

The research has been supported by the Georgia Research Alliance (GRA), the Ovarian Cancer Institute, the Robinson Family Foundation and the Deborah Nash Harris Endowment. A member of Georgia Tech’s Advanced Technology Development Center (ATDC) startup accelerator program and a GRA VentureLab company, Sub-Micro has also raised private funding to support its prototype development.

Challenges ahead include ensuring that nanoparticles cannot bypass the filtration system to enter the body, and controlling the risk of infection caused by opening the peritoneal cavity.

Beyond cancer, the researchers believe their approach could be useful for treating other diseases in which a reduction in circulating cancer cells or virus particles could be useful. Using magnetic nanoparticles engineered to capture HIV could help reduce viral content in the bloodstream, for instance.

“A technology like this has many different possibilities,” said Scarberry. “We are currently developing the technology to control the metastatic spread of ovarian cancer, but once we have a device that can efficiently and effectively isolate cancer cells from circulating fluids, including blood, we would have other opportunities.”

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Outside-the-Box: The Rogosin Institute Is Fighting Cancer With Cancer Cells In Clinical Trials

Researchers at the Rogosin Institute are using cancer “macrobeads” to fight cancer.  Cancer cells in the beads secrete proteins which researchers believe could signal a patient’s cancer to stop growing, shrink or even die. The treatment is currently being tested in human clinical trials.

Two groundbreaking preclinical studies demonstrate for the first time that encapsulated mouse kidney cancer cells inhibit the growth of freely-growing cancer cells of the same or different type in a laboratory dish and in tumor-bearing animals. These findings support the hypothesis that cancer cells entrapped in seaweed-based gel, called “macrobeads,” send biological feedback or signals to freely-growing tumors outside the macrobead to slow or stop their growth. Both studies (cited below) are published in the on-line January 24, 2011 issue of Cancer Research, a publication of the American Association For Cancer Research.

Barry H. Smith, M.D., Ph.D., Director, The Rogosin Institute; Professor, Clinical Surgery, Weill Cornell Medical College

The Rogosin Institute, an independent not-for-profit treatment and research center associated with New York-Presbyterian Hospital and Weill Cornell Medical College, developed the cell encapsulation technology that facilitated production of the macrobead and applied this technology in conducting preclinical studies. The research team was headed by Barry H. Smith, M.D., Ph.D.,  the Director of The Rogosin Institute, Professor of Clinical Surgery at the Weill Cornell Medical College, and lead author of the studies. Findings in the studies to date are consistent with the hypothesis that when macrobeads are implanted in a host, the encapsulated cells are isolated from the host’s immune system but continue to maintain their functionality.

In addition to the standard preclinical in vivo and in vitro experiments, a clinical veterinary study was conducted in cats and dogs suffering from various spontaneous (non-induced) cancers. More than 40 animals were treated with the macrobead technology. Consistent results, measured both in terms of tumor response and animal well-being, occurred with prostate, liver and breast cancer, as well as lymphoma. Additional research revealed that regardless of the animal specie or type of cancer cell that was encapsulated, the macrobead technology inhibited cancer growth across all species and cancer types tested.  The results have included slowed tumor growth or, in some cases, necrosis and elimination of tumors and the restoration of a normal animal lifespan.

Cancer macrobead therapy has proceeded to human clinical testing. A Phase 1 trial in more than 30 patients evaluated the safety of macrobeads implanted in the abdominal cavity as a biological treatment of end-stage, treatment-resistant, epithelial-derived cancer. Based on the safety profile data, Phase 2 efficacy trials are in progress in patients with colorectal cancer, pancreatic cancer and prostate cancer. The Phase 1 trial remains open to a range of epithelial-derived cancers, including ovarian.  To date, the Rogosin Institute research team has not found evidence to indicate that placing mouse tumors in humans or other animal species causes harm or side-effects.

Scientists are testing whether macrobeads containing cancer cells can be implanted into patients and communicate with the patient’s tumor to stop growing, shrink or die.

Step 1:  Small beads are made from a seaweed-derived sugar called agarose and mixed with 150,000 mouse kidney cancer cells, and a second layer of agarose is added, encapsulating the cancer cells.

Step 2:  Within 3-to-10 days, 99% of the kidney cancer cells die.  The remaining cells have traits similar to cancer stem cells.

Step 3:  The stem cells begin to recolonize the bead.  The colonies increase in sufficient numbers within a few weeks to reach a stable state.

Step 4:  The beads begin to release proteins —  chemical signals reflecting that the beads have sufficient numbers of cells for growth regulators to kick in.

Step 5: Several hundred beads (depending on patient’s weight) are implanted in the abdominal cavity in a laparoscopic surgical procedure.  The cancer cells are trapped in the beads; preventing their circulation elsewhere in the body and protecting them from attack by the body’s immune system.

Step 6: In animal studies, researchers believe some proteins released from the beads reached tumors elsewhere in the body and tricked them into sensing that other tumor cells are nearby.

Step 7:  As a result, researchers believe tumors in some animals stopped growing, shrank or died.  The hypothesis is being tested in people with cancer.

Howard Parnes, M.D., Chief, Prostate & Urologic Cancer Research Group, Division of Cancer Prevention, National Cancer Institute

“This is a completely novel way of thinking about cancer biology,” says Howard L. Parnes, a researcher in the Division of  Cancer Prevention at the National Cancer Institute who is familiar with the work but was not involved with it. “We talk about thinking outside the box. It’s hard to think of a better example.” “They demonstrate a remarkable proof of principle that tumor cells from one animal can be manipulated to produce factors that can inhibit the growth of cancers in other animals,” Dr. Parnes says. “This suggests that these cancer inhibitory factors have been conserved over millions of years of evolution.”

“Macrobead therapy holds promise as a new option in cancer treatment because it makes use of normal biological mechanisms and avoids the toxicities associated with traditional chemotherapy,” said Dr. Barry Smith. “The results of our research show that this approach is not specific to tumor type or species so that, for example, mouse cells can be used to treat several different human tumors and human cells can be used to treat several different animal tumors.”

“Because cancer and other diseases are their own biological systems, we believe that the future of effective disease treatment must likewise be biological and system-based,” said Stuart Subotnick, CEO of Metromedia Bio-Science LLC. “Many of the existing therapies are narrow, targeted approaches that fail to treat diseases comprehensively. In contrast, our unique macrobead technology delivers an integrated cell system that alters disease processes and utilizes the body’s natural defense mechanisms. The goal is to repair the body and not merely treat the symptoms.”

It is well-known that proof of anti-tumor activity in treating animals does not represent guaranteed effectiveness in humans. But, assuming the macrobead therapy proves ultimately effective in humans, it would represent a novel approach to treating cancer and challenge existing scientific dogmas.

The cancer macrobead therapy described above is backed by Metromedia Company, a privately held telecommunications company which was run by billionaire John Kluge until his recent death. The Metromedia Biosciences unit has invested $50 million into the research.  If the treatment proves successful in humans, a large part of the revenue generated will be contributed to Mr. Kluge’s charitable foundation.

About Metromedia Bio-Science LLC

Metromedia Bio-Science LLC, in conjunction with The Rogosin Institute, utilizes the novel cell encapsulation technology to conduct research into the treatment of various diseases, including cancer and diabetes, and the evaluation of disease therapies. Metromedia Bio-Science LLC is an affiliate of Metromedia Company, a diversified partnership founded by the late John W. Kluge and Stuart Subotnick.

About The Rogosin Institute

The Rogosin Institute is an independent not-for-profit treatment and research center associated with New York-Presbyterian Hospital (NYPH) and Weill Cornell Medical College. It is one of the nation’s leading research and treatment centers for kidney disease, providing services from early stage disease to those requiring dialysis and transplantation. It also has programs in diabetes, hypertension and lipid disorders. The Institute’s cancer research program, featuring the macrobeads, began in 1995. The Rogosin Institute is unique in its combination of the best in clinical care with research into new and better ways to prevent and treat disease.

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Libby’s H*O*P*E*™ Proudly Announces A Strategic Partnership With Women’s Oncology Research & Dialogue

It is our privilege and honor to announce a strategic partnership between Libby’s H*O*P*E*™ and Women’s Oncology Research & Dialogue.

It is our privilege and honor to announce a strategic partnership between Libby’s H*O*P*E*™ (LH) and Women’s Oncology Research & Dialogue (WORD). WORD’s overarching mission is to raise gynecologic cancer awareness and fund related scientific research.

The genesis of this partnership began approximately one year ago, when LH was contacted by Nathan Manahan, WORD’s Executive Director. WORD had performed extensive social media due diligence and determined that LH was a premier source of online ovarian cancer information.  As the LH Founder, I agreed to meet Nate and Chad Braham (WORD’s Director of Media Productions) in Los Angeles to discuss the possibility of both organizations working together.

I felt an immediate connection with Nate and Chad, especially after we discussed the personal reasons underlying our passion for cancer advocacy.  Nate explained that his mother was a breast cancer survivor, who battled the disease successfully due to vigilance, which caught her aggressive cancer at an early stage. It also happens that Nate’s sister is Dr. Kelly J. Manahan, WORD’s Founder and President. Chad discussed how he lost his father to cancer when he was 8 years old, along with the fact that his stepfather is a prostate cancer survivor, and his mother-in-law is a uterine cancer survivor (who was successfully treated by Dr. Manahan).

By the end of that initial meeting, we believed that a strategic partnership between both organizations would be highly synergistic. Although WORD advocates on behalf of women with all gynecologic cancers, it has designated LH as its “go-to” source for detailed ovarian cancer information. In turn, LH obtains a greater audience for its ovarian cancer advocacy by communicating to women interested in learning more about all gynecologic cancers through the new WORD website.

As a kickoff to our partnership, WORD created nine short videos about the genesis of LH, its mission, the credibility & understandability of the LH website, the early warning signs of ovarian cancer, LH assistance to ovarian cancer survivors, survivor success stories, the fast pace of medical research, and a brief discussion of the LH/WORD partnership. The LH/WORD partnership video is provided below. We will post the remaining eight videos over the next two weeks.

In the near future, we anticipate the creation and distribution of an ongoing video podcast series known as WORD of HOPE, which will address important ovarian cancer topics in an easily understandable format.

We are quite excited about the opportunities presented by this partnership, and hope to build upon the LH/WORD alliance for many years to come.

“The challenge of every team is to build a feeling of oneness, of dependence on one another because the question is usually not how well each person performs, but how well they work together.”

— Vince Lombardi (1913 – 1970), former Head Coach of the National Football League (NFL) Green Bay Packers & Winner of 5 NFL Championships, including Super Bowls I & II.

The Genesis of WORD

Drs. Kelly J. Manahan & John P. Geisler, Co-Founders, Women's Oncology Research & Dialogue (WORD)

Several years ago, as a gynecologic oncologist in training, Dr. Manahan learned first-hand that cancer is a formidable foe. This experience compelled her to take greater action.  In Fall 2005, Dr. Manahan established WORD, along with her husband Dr. John P. Geisler.  Currently, Dr. Manahan is the Interim Chair of the Department of Obstetrics and Gynecology at the University of Toledo Medical Center (UTMC), while Dr. Geisler is Director of  Gynecologic Oncology and Chief of Clinical Service Obstetrics & Gynecology at UTMC.  Dr. Geisler is also the Chairman of the WORD medical advisory panel.  Drs. Manahan and Geisler are both gynecologic oncologists, and are cited as authors in approximately 85 published medical articles relating to a wide array of gynecologic oncology topics.  Such topics include cutting-edge surgical techniques and novel gynecological cancer treatments.

WORD was founded with the mission of spreading global gynecological cancer awareness.  WORD exists to educate; to inform, to bring awareness, to teach prevention, and assist women who have been diagnosed with a gynecologic cancer. The passion of the WORD team is to provide women and their families with relevant, detailed, and up-to-date information that can save lives. In sum, WORD was formed to help win the fight against gynecologic cancers.

Past and present WORD research projects and initiatives include:

  • a study of hydralazine and megestrol acetate to treat advanced, chemoresistant cancers of the ovary, peritoneum, uterus, fallopian tube, cervix, and vulva;
  • a tissue bank of clinically annotated tissue specimens from patients with gynecologic cancers.

“We are a husband and wife team who have both been helping women battle gynecologic cancers for over two decades,” said Dr. Manahan. “Our passion is helping women have complete understanding when facing the battle of their cancer. We also want women to be empowered to make lifestyle and health decisions that can work to prevent cancer.”

“Our goal is to assure that all women are more aware of these diseases and to find a way to increase prevention, early detection, and optimal treatment,” said Dr. Geisler. “Awareness will lead to more research dollars. More research will hopefully lead to finding the detailed factors that influence the growth of these diseases. We ultimately want a cure. Wordoncancer.org is the integral foundation to many of these dreams.”

“I am a member of a team, and I rely on the team, I defer to it and sacrifice for it, because the team, not the individual, is the ultimate champion.”

— Mia Hamm, who is widely recognized as the world’s best all-around women’s soccer player (2 Olympic Gold Medals & 2 World Championships).

WORD’s New Website Launch

The average woman in the United States has a 1-in-12 risk factor of developing a gynecologic cancer in her lifetime. On November 9, 2010, WORD launched their new website at http://www.wordoncancer.org. WORD’s new website will inform women about preventions, signs, symptoms, diagnosis and treatment of all gynecologic cancers. WORD’s website will inspire women to take actions that can, and will, save their lives, and was designed to expand and grow as new data and relevant information become available.

Today, most people do their research online. Accordingly, WORDoncancer.org was designed to achieve the overarching goals listed below.

  • Provide the best gynecologic cancer web video content, including survivor stories, expert advice provided by various medical professionals, and stories from families who have lost loved ones.
  • Guarantee current information about the prevention, diagnosis and treatment of gynecologic cancers, which is created in a simple and user-friendly interface.
  • Create pathways to dialogue among women and their physicians, so every woman is empowered to make an informed decision about her health care.
  • Utilize the most effective and relevant multimedia tools to accomplish our organizational mission.
  • Connect and create partnerships with grassroots groups throughout the United States, empowering them to create local efforts to conquer gynecologic cancers.

A few of the key highlights of the new site are listed below.

  • Animation – WORD sanctioned the creation of a 4-minute animated short story entitled, WORD on HPV (watch video below).
  • Formal launch of the Let’s Talk Video SeriesLet’s Talk is a personal history campaign aimed at archiving the stories of women who have battled gynecologic cancer. WORD has collected and edited many of these stories and the collection is available on WORD’s YouTube™ channel and throughout the copy on the website.

  • New Expert WORDS of Wisdom Video Series – WORD will work to create video vignettes to help women better understand gynecologic cancer prevention, diagnosis, and treatment. These videos will provide a complimentary explanation to web content and are also housed on WORD’s YouTube™ channel.

  • Targeted Campaign for 18-24 year old women regarding cervical cancer/human papillomavirus (HPV) – WORD is utilizing recently conducted research to create a personalized campaign for 18-24 year old young women to get the HPV vaccine and begin proper cancer prevention.
  • WORD Blog, FacebookTwitter – For readers “on-the-go,” make sure that you monitor significant WORD news and updates through its blog, Facebook page and Twitter account.

Coming together is a beginning; keeping together is progress; working together is success. — Henry Ford, Founder of the Ford Motor Company

WORD Initiates a “Dialogue” During Cervical Health Awarenss Month.

“Those of us who work and volunteer with WORD know that the dialogue we create will often be controversial. The conversations we hope to create are critical, personal and sometimes intimidating. We are dealing with topics that have real and severe consequences. Often what we say may not be received well; our goal is not acceptance but dialogue. We want women to rise up and become advocates for their own health care. We want women to ask questions, the hard questions, to make sure they make the best informed decisions about their health. We want women to be respectful – staying true to their own convictions, but standing united through dialogue in one common purpose – ‘We must conquer cancer!'”

— Nathan Manahan, WORD Executive Director

This year, Over 11,000 American women will learn that they have cervical cancer, and nearly 4,000 will die from the disease. Tens of thousands more women will have precancerous cells treated.  January is designated as Cervical Health Awareness Month, which is intended to aid in the prevention and early detection of cervical cancer.  This month, WORD is committed to raising awareness of this preventable, detectable and treatable disease among all women in the United States.

One of the most controversial and uncomfortable subjects that WORD seeks to start dialogue on is the cause of cervical cancer, namely HPV.  HPV is a sexually transmitted infection that causes cervical cancer among other cancers and health problems.  In 2010, WORD set out to create an effective HPV and cervical cancer women’s health education campaign. In short, WORD wants to make sure that women of all ages can make informed health decisions about the HPV vaccine, annual gynecological exams, Pap tests and the HPV test. Through a series of excellent partners including Purdue University, David Bossert of Madison Beach Productions, Duck Studios and Publicis Group, WORD was able to create a comprehensive health education program.

In 2011, WORD is working toward an extremely ambitious but necessary goal: distribution of life-saving HPV/cervical information to 30 cities located in 15 states. “This campaign is the first of many campaigns to be created by the WORD team,” said Nate Manahan. “WORD hopes to partner with many individuals and organizations to see these new resources used in communities throughout the United States and ultimately the world.”

WORD encourages individuals and organizations to see how they might utilize the WORD on HPV campaign resources throughout the next year. This campaign includes an original four minute animated short story (view below), posters, brochures, magnets, rack cards, 30 and 60 second radio spots, 15 and 30 second television spots, and informative survivor and expert videos. In addition, WORD is participating in the Cervical Cancer Free America initiative (CCFA), which is is a multi-year, multi-state project aimed at preventing the disease through vaccination against HPV and effective screening for early signs of cervical cancer. WORD is proud to announce that the Cervical Cancer Free Indiana initiative is utilizing many of the WORD on HPV resources in 2011, through a collaboration with the Kristen Forbes EVE Foundation.

“WORD on HPV” Animated Short Story

Regular administration of Pap tests is the best means of detecting cervical cancer at an early stage. The addition of the HPV test further advances our ability to detect cervical cancer early. Furthermore, HPV vaccines have the potential to protect women from the disease, by targeting cancer-causing types of the HPV. “With the advancement of the HPV vaccine in women’s health and in cancer prevention, we may have the first opportunity to literally eradicate cervical cancer,” said Dr. Geisler. “We are all hopeful that between the vaccines, Pap tests and the HPV test, we will see the eradication of cervical cancer around the world in our lifetime.”

In further support of WORD’s overarching vision, Dr. Sharmila Makhija, Division Director of Gynecologic Oncology at Emory University said:

“WORD’s vision to offer resources and education to women of all ages to promote dialogue on prevention, diagnosis and treatment of gynecologic cancers (cervical, uterine and ovarian) is important and something I wholeheartedly support and encourage all individuals and organizations to support.”

About Women’s Oncology Research & Dialogue

WORD is an Indianapolis-based nonprofit organization dedicated to helping women conquer gynecologic cancers through coordinating innovative scientific and clinical research, which results in empowering educational resources for women’s organizations and medical personnel regarding proper prevention, diagnosis and treatment. They need your support to help spread awareness and raise money to help conquer gynecologic cancer.

More information can be found online at http://www.wordoncancer.org/media, including WORD’s informative brochures regarding (i) gynecologic cancer, (ii) ovarian cancer, (iii) cervical cancer, and (iv) uterine cancer.

If you are interested in making a donation to WORD, please go to http://wordoncancer.org/cms/word-site/get-involved/donate.

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Caris Life Sciences Launches Molecular Profiling Service For Ovarian Cancer Patients

Caris Life Sciences announces the launch of a new molecular profiling service for ovarian cancer patients

Caris Life Sciences, Inc. (Caris), a leading biosciences company focused on enabling precise and personalized healthcare through the highest quality anatomic pathology, molecular profiling, and blood-based diagnostic services, announced the launch of a new, Caris Target Now™ molecular profile for ovarian cancer patients. This expansion of the Caris Target Now™ offering provides individualized molecular information to treating physicians, relevant to the selection of therapies to treat this highly-lethal cancer. Ovarian cancer affects more than 20,000 women annually and produces some of the highest five-year mortality rates found among the 200+ types of cancer.

Caris Target Now™ molecular profiling examines the unique genetic and molecular make-up of each patient’s tumor so that treatment options may be matched to each patient individually.  Caris Target Now™ helps patients and their treating physicians create a cancer treatment plan based on the tumor tested. By comparing the tumor’s information with data from published clinical studies by thousands of the world’s leading cancer researchers, Caris can help determine which treatments are likely to be most effective and, just as important, which treatments are likely to be ineffective.

The Caris Target Now™ test is performed after a cancer diagnosis has been established and the patient has exhausted standard of care therapies or if questions in therapeutic management exist. Using tumor samples obtained from a biopsy, the tumor is examined to identify biomarkers that may have an influence on therapy. Using this information, Caris Target Now™ provides valuable information on the drugs that will be more likely to produce a positive response. Caris Target Now™ can be used with any solid cancer such as lung cancer, breast cancer, prostate cancer, and now, ovarian cancer.

Evidence Behind Caris Target Now™

Daniel D. Von Hoff, M.D., F.A.C.P., is the Executive Director of Caris Life Sciences' Clinical Research

A multi-center, prospective, pilot study first published in The Journal of Clinical Oncology (JCO) in October 2010 [1] — along with an accompanying editorial [2] —  determined that personalized cancer treatment tailored to a tumor’s unique genetic make-up identified therapies that increased progression free survival (PFS) over previous therapies in 27% of patients with advanced disease.

The purpose of the study was to compare PFS using a treatment regimen based on the molecular profiling (MP) of a patient’s tumor with the PFS determined for the most recent regimen on which the patient had experienced progression after taking that regimen for 6 weeks.  Unlike a typical control study, each patient was his or her own study control.  Tissue samples from patients with refractory metastatic cancer were submitted for MP in two formats including:

In many of these refractory tumors, targets for conventional therapies were identified, which was “a surprise finding,” according to Dr. Daniel Von Hoff, the Executive Director of Caris’ Clinical Research.  But the profiling also suggested therapies in cases where the treating physician was unsure regarding the next line of treatment. The MP approach was found to have clinical benefit for the individual patient who had a PFS ratio (PFS on MP selected therapy/PFS on prior therapy) of ≥ 1.3.  Among the 86 patient tumors that were profiled with Caris Target Now™:

  • 84 (98%) had a detected molecular target;
  • 66 of the 84 patients were treated with therapies that were linked to their MP results; and
  • 18 (27%) of 66 patients had a PFS ratio of ≥ 1.3 (95% CI, 17% to 38% range; one-sided, one-sample P = .007).

The study investigators concluded that it is possible to identify molecular targets in patients’ tumors. In 27% of the patients, the MP approach resulted in a longer PFS on a MP-based regimen than on the regimen that was based on physician’s choice.  “It was also encouraging to see that the overall survival in these 18 patients was better than that for the whole group of 66 patients (9.7 vs. 5 months),” said Von Hoff.

Of the 66 participants, 27% had breast cancer, 17% had colorectal cancer, and 8% had ovarian cancer; the remainder were classified as miscellaneous.  The improvement in PFS among the various types of cancer patients was as follows: 44% in patients with breast cancer, 36% in those with colorectal cancer, 20% in those with ovarian cancer, and 16% in the miscellaneous group.

The investigators in the study utilized Caris Target Now™ molecular profiling, which is currently available to oncologists and their patients.

“Oncologists commonly expect a 1-in-20 chance of patient response in 3rd- and 4th-line therapies.  This recent study suggests those odds can be improved to 1-in-4 when using therapeutic guidance provided by Caris Target Now™.”

Dr. Jeff Edenfield, a practicing oncologist with US Oncology, and routine user of Caris Target Now™

Since 2008, more than 15,000 cancer patients have received a Caris Target Now™ molecular profile. Caris Target Now™ has been designed to provide treating physicians with therapeutic options, often identifying anti-tumor agents that may not have been considered before. The Caris Target Now™ report is based on the genetic make-up of an individual patient’s tumor cross-referenced with a vast and growing proprietary database of clinical literature, correlating genetic tumor information to therapeutic response. Using biomarker-based therapies has been linked to the likelihood of a positive patient response.

James H. Doroshow, M.D., Director, Division of Cancer Treatment & Diagnosis, National Cancer Institute

In the accompanying JCO editorial, James H. Doroshow, M.D., the Director of the National Cancer Institute (NCI) Division of Cancer Treatment and Diagnosis, commented that the study by Von Hoff et. al. possessed several limitations. [2] The stated limitations of the study include (i) uncertainty surrounding the achievement of the study’s primary end point based upon use of the time-to-disease progression (TTP) index; (ii) limited prior experience with patients as their own controls, and (iii) lack of study randomization.  Despite these limitations, Dr. Doroshow noted that important lessons can be learned from the study conducted by Von Hoff et. al.

“First and foremost, this study vividly reminds us that the need for therapeutic intervention arises one patient at a time. When we sit with an individual who is trying to live with an advanced solid tumor after having already received several different chemotherapy regimens, it is unlikely that any published prognostic index or gene signature, as currently implemented, will be of much help in decision making—for physicians or for patients. [citation omitted]. Thus, a truly urgent need exists to move past the empiric therapeutic paradigm that launched the first half century of systemic oncologic treatment. [citation omitted]. Von Hoff et al have taken a noteworthy, albeit somewhat flawed, first step in this direction in their attempt to imagine a novel paradigm for cancer therapy, using the techniques of molecular tumor characterization on an individual patient basis. Future investigators of new cancer therapies should learn from this initial effort and focus on how these rapidly evolving molecular tools can be used in the development of an entirely new investigative model for the systemic treatment of cancer.”

Caris is currently conducting and initiating additional studies of Caris Target Now™ molecular tumor profiling through collaboration with leading institutions and cancer centers. 

With 300% growth in utilization in 2010, medical oncologists are recognizing the utility and value of this novel approach in providing improved care to patients. Physician adoption is rapidly accelerating, as Caris recently reached the threshold of providing Caris Target Now™ services to more than 1,000 patients per month. This new introduction for ovarian cancer is most relevant for physicians treating women who have progressed on platinum-based therapy and/or who need guidance for third-line treatment options. Caris Target Now™ for ovarian cancer offers the opportunity for these women to benefit from personalized and targeted therapy guidance based upon molecular profiling.

“Ovarian cancer is a highly-lethal cancer that presents distinct diagnostic and therapeutic challenges, often presenting no major symptoms until the cancer has metastasized,” said Dr. Les Paul, Caris’ Senior Vice President for Medical Affairs. “Choosing the optimal therapeutic intervention at the earliest possible stage is critical to extending progression free survival in ovarian cancer patients. With the introduction of the Caris Target Now™ ovarian profile, we are able to support physicians with as much information as possible, including the latest relevant clinical literature citations to aid them in making the best therapeutic decision possible for each patient.”

Examples of the potential use of an existing clinical trial drug to target a specific molecular characteristic possessed by an ovarian cancer include:

Use of Molecular Profiling By Leading Medical Institutions; Sponsorship By A Charitable Foundation

It should be noted that molecular profiling is already being used in clinical practice at several leading cancer institutions.  At Massachusetts General Hospital, (MGH), The MGH Cancer Centre uses a PCR-based mutation-detection assay and state-of-the-art robotic technology, called “SNaPshot,” to look for 130 known gene mutations in tumor tissue. “We are already using molecular profiling for all our lung cancer patients,” said Jeffrey Settleman, Ph.D., scientific director at the MGH Cancer Center, to Medscape Oncology in 2009. [12] “This has already had an impact on treatment decisions, and it appears to be improving treatment. We have seen better response rates and we hope that this will translate into better survival.”  In fact, MGH is engaged currently in the largest study aimed at matching tumor genomes to potential anticancer treatments. [13] It is our understanding that MGH performs molecular profiling currently on melanoma, leukemia, brain and metastatic breast cancer, and metastatic adenocarcinoma that start in the lung, colon or rectum.

Several other institutions are in the process of developing or have developed their own systems, including the University of Texas M.D. Anderson Cancer Center [14], and the Dana-Farber Cancer Institute [15].  All are striving to profile individual tumors so that therapy can be personalized, which means that it has a better chance of working because it targets specific mutations found in a patient’s tumor. The MP approach also prevents patients from being exposed to drugs that have a limited chance of success, eliminating toxicity and improving quality of life.

We should also note the Clearity Foundation sponsors molecular profiling services on behalf of ovarian cancer patients at no cost. The Clearity Foundation is a 501(c)(3) not-for-profit, founded by Laura Shawver, Ph.D., who is an ovarian cancer survivor and research scientist.  The Clearity Foundation seeks to improve treatment outcomes in recurrent and progressive ovarian cancer patients by providing diagnostic services that determine the molecular profile of the individual patient with the belief that a molecular “blueprint” is crucial to finding appropriate treatments.

About Caris Target Now™

Caris Target Now™ is a comprehensive tumor analysis coupled with an exhaustive clinical literature search, which matches appropriate therapies to patient-specific biomarker information to generate an evidence-based treatment approach. Caris Target Now™ testing provides information that may help when considering potential treatment options.

Caris Target Now™ begins with an immunohistochemistry (IHC) analysis. An IHC test measures the level of important proteins in cancer cells providing clues about which therapies are likely to have clinical benefit and then what additional tests should be run.

If there is access to a frozen sample of patient tissue available, Caris may also run a gene expression analysis by microarray. The microarray test looks for genes in the tumor that are associated with specific treatment options.

As deemed appropriate based on each patient, Caris will run additional tests. Fluorescent In-Situ Hybridization (FISH) is used to examine gene copy number variation (i.e., gene amplification) in the tumor. Polymerase Chain Reaction (PCR) or DNA sequencing is used to determine gene mutations in the tumor DNA.

Caris takes the results from each test and applies the published findings from thousands of the world’s leading cancer researchers. Based on this analysis, Caris Target Now™ identifies potential therapies for patients and their treating physicians to discuss.

Caris Target Now™ was developed and its performance characteristics were determined by Caris, a CLIA-certified medical laboratory in compliance with the U.S. Clinical Laboratory Amendment Act of 1988 and all relevant U.S. state regulations. It has not been approved by the United States Food and Drug Administration.

About Caris Life Sciences

Caris Life Sciences, a leading biosciences company, specializes in the development and commercialization of the highest quality anatomic pathology, molecular profiling, and blood-based diagnostic technologies, in the fields of oncology, dermatopathology, hematopathology, gastrointestinal pathology and urologic pathology. The company provides academic-caliber consultations for patients every day, through its industry-leading team of expert, subspecialty pathologists. Caris also offers advanced molecular analyses of patient samples through prognostic testing services and genomic, transcriptomic, and proteomic profiling to assist physicians in their treatment of cancer. Currently, Caris is developing the Carisome™ platform, a proprietary, blood-based technology for diagnosis, prognosis, and theranosis of cancer and other complex diseases. The company is headquartered in the Dallas metroplex, and operates laboratories at the headquarters, as well as in the Phoenix and Boston metro areas.

About Daniel Von Hoff, M.D., FACP, Executive Director, Caris Life Sciences Clinical Research

Daniel D. Von Hoff, M.D., is currently physician-in-chief and director of translational research at Translational Genomics Research Institute (TGen) in Phoenix, Arizona. He is also chief scientific officer for US Oncology and the Scottsdale Healthcare’s Clinical Research Institute.  He holds an appointment as clinical professor of medicine at the University of Arizona College of Medicine.

Dr. Von Hoff’s major interest is in the development of new anticancer agents, both in the clinic and in the laboratory. He and his colleagues were involved in the beginning of the development of many of the agents now in routine use, including: mitoxantrone, fludarabine, paclitaxel, docetaxel, gemcitabine, irinotecan, nelarabine, capecitabine, lapatinib and others.

At present, Von Hoff and his colleagues are concentrating on the development of molecularly targeted therapies particularly for patients with advanced pancreatic cancer. Dr. Von Hoff’s laboratory interests and contributions have been in the area of in vitro drug sensitivity testing to individualize treatment for the patient, mechanisms of gene amplification, particularly of extrachromosomal DNA, and understanding of and targeting telomere maintenance mechanisms. His laboratory work now concentrates on the discovery of new targets in pancreatic cancer.

Dr. Von Hoff has published more than 543 papers, 133 book chapters, and more than 956 abstracts. Dr. Von Hoff  also served on President Bush’s National Cancer Advisory Board from June 2004 through March 2010.

Dr. Von Hoff is the past president of the American Association for Cancer Research(AACR) (the world’s largest cancer research organization), a fellow of the American College of Physicians, and a member and past board member of the American Society of Clinical Oncology (ASCO). He is a founder of ILEX™ Oncology, Inc. (acquired by Genzyme after Ilex had 2 agents, alemtuzumab and clofarabine approved for patients with leukemia). He is founder and the editor emeritus of Investigational New Drugs – The Journal of New Anticancer Agents; and, editor-in-chief of Molecular Cancer Therapeutics. He is also proud to have been a mentor and teacher for multiple medical students, medical oncology fellows, graduate students, and post-doctoral fellows. He is a co-founder of the AACR/ASCO Methods in Clinical Cancer Research Workshop.

References:

1/ Von Hoff DD, Stephenson JJ Jr, Rosen P, et. al. Pilot study using molecular profiling of patients’ tumors to find potential targets and select treatments for their refractory cancers. J Clin Oncol. 2010 Nov 20;28(33):4877-83. Epub 2010 Oct 4. PubMed PMID: 20921468.

2/ Doroshow JH. Selecting systemic cancer therapy one patient at a time: Is there a role for molecular profiling of individual patients with advanced solid tumors? J Clin Oncol. 2010 Nov 20; 28(33):4869-71. Epub 2010 Oct 4. PMID: 20921466.

3/Addition of Dasatinib (Sprycel) to Standard Chemo Cocktail May Enhance Effect in Certain Ovarian Cancers, by Paul Cacciatore, Libby’s H*O*P*E*™, April 19, 2009.

4/UCLA Researchers Significantly Inhibit Growth of Ovarian Cancer Cell Lines With FDA-Approved Leukemia Drug Dasatinib (Sprycel®), by Paul Cacciatore, Libby’s H*O*P*E*™, November 11, 2009.

5/BMS-345541 + Dasatinib Resensitizes Carboplatin-Resistant, Recurrent Ovarian Cancer Cells, by Paul Cacciatore, Libby’s H*O*P*E*™, July 1, 2010.

6/PARP Inhibitor Olaparib Benefits Women With Inherited Ovarian Cancer Based Upon Platinum Drug Sensitivity, by Paul Cacciatore, Libby’s H*O*P*E*™, April 23, 2010.

7/ Fong PC, Boss DS, Yap TA, et al. Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriersN Engl J Med. 2009 Jul 9;361(2):123-34. Epub 2009 Jun 24. PMID: 19553641.

8/Audeh MW, Penson RT, Friedlander M, et al. Phase II trial of the oral PARP inhibitor olaparib (AZD2281) in BRCA-deficient advanced ovarian cancer. J Clin Oncol 2009;27(supplement):p. 15S.

9/PARP Inhibitor MK-4827 Shows Anti-Tumor Activity in First Human Clinical Study, by Paul Cacciatore, Libby’s H*O*P*E*™,  November 17, 2010.

10/PI3K Pathway: A Potential Ovarian Cancer Therapeutic Target?, by Paul Cacciatore, Libby’s H*O*P*E*™,  November 20, 2009.

11/Endocyte’s EC145 Produces Significant Anti-Tumor Activity In Advanced Stage Chemoresistant Ovarian Cancer Patients, by Paul Cacciatore, Libby’s H*O*P*E*™, October 21, 2009.

12/Massachusetts General Hospital Cancer Center To Genetically Profile All Patient Tumors, by Paul Cacciatore, Libby’s H*O*P*E*™, March 14, 2009.

13/Largest Study Matching Genomes To Potential Anticancer Treatments Releases Initial Results, by Paul Cacciatore, Libby’s H*O*P*E*™, August 3, 2010.

14/An Initiative for Molecular Profiling in Advanced Cancer Therapy (IMPACT) Trial. A Molecular Profile-Based Study in Patients With Advanced Cancer Treated in the Investigational Cancer Therapeutics Program, University of Texas M.D. Anderson Cancer Center, ClinicalTrials.gov Identifier: NCT00851032.

15/Dana-Farber Researchers “OncoMap” The Way To Personalized Treatment For Ovarian Cancer, by Paul Cacciatore, Libby’s H*O*P*E*™, November 16, 2010.

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Additional Information:

National Comprehensive Cancer Network® Posts New Guidelines for Treatment of Ovarian Cancer Patients

National Comprehensive Cancer Network® Posts New “Patient Friendly” Guidelines for Treatment of Ovarian Cancer.

Women with ovarian cancer now have a new resource that provides them with the same credible information their physicians use when determining treatment options. The National Comprehensive Cancer Network® (NCCN®) announces three new additions to the library of NCCN Guidelines for Patients™, patient-friendly translations of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™). NCCN Guidelines for Patients™: Melanoma, Ovarian Cancer, and Prostate Cancer are now available free of charge at NCCN.com.

The NCCN Guidelines for Patients™ are designed to provide people with cancer and their caregivers with state-of-the-art treatment information in easy-to-understand language. Given the prevalence of melanoma and prostate cancer – both among the most frequently diagnosed cancers in men – and the challenges in detecting ovarian cancer in women, it is critical that patients have resources to empower them to take a more active role in their treatment.

The NCCN Guidelines™ are developed by multidisciplinary panels of experts from NCCN Member Institutions and feature algorithms or “decision trees” that address every appropriate treatment option from initial work up throughout the course of the disease. The NCCN Guidelines for Patients™ translate these professional guidelines in a clear, step-by-step manner that patients can use as the basis for making decisions and discussing options with their physicians.

The NCCN Guidelines for Patients™ are available free of charge at NCCN.com, which also features additional informative articles for patients and caregivers.

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.

The NCCN Member Institutions are:

City of Hope Comprehensive Cancer Center, Los Angeles, CA;

Dana-Farber/Brigham and Women’s Cancer Center | Massachusetts General Hospital Cancer Center, Boston, MA;

Duke Comprehensive Cancer Center, Durham, NC;

Fox Chase Cancer Center, Philadelphia, PA;

Huntsman Cancer Institute at the University of Utah, Salt Lake City, UT;

Fred Hutchinson Cancer Research Center/Seattle Cancer Care Alliance, Seattle, WA;

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD;

Robert H. Lurie Comprehensive Cancer Center of Northwestern University, Chicago, IL;

Memorial Sloan-Kettering Cancer Center, New York, NY;

H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL;

The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute, Columbus, OH;

Roswell Park Cancer Institute, Buffalo, NY;

Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, St. Louis, MO;

St. Jude Children’s Research Hospital/University of Tennessee Cancer Institute, Memphis, TN;

Stanford Comprehensive Cancer Center, Stanford, CA;

University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL;

UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA;

University of Michigan Comprehensive Cancer Center, Ann Arbor, MI;

UNMC Eppley Cancer Center at The Nebraska Medical Center, Omaha, NE;

The University of Texas MD Anderson Cancer Center, Houston, TX; and

Vanderbilt-Ingram Cancer Center, Nashville, TN.

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Lab-On-A-Chip: Veridex & MGH Collaborate On Next-Generation Circulating Tumor Cell Test

Veridex, LLC announces a collaboration with Massachusetts General Hospital to develop and commercialize a next-generation circulating tumor cell technology for capturing, counting and characterizing tumor cells found in patients’ blood.

Yesterday, Veridex, LLC (Veridex) announced a collaboration with Massachusetts General Hospital (MGH) to develop and commercialize a next-generation circulating tumor cell (CTC) technology for capturing, counting and characterizing tumor cells found in patients’ blood. The collaboration will involve Ortho Biotech Oncology Research & Development (ORD), a unit of Johnson & Johnson Pharmaceutical Research & Development. It focuses on the development of a next-generation system that will enable CTCs to be used both by oncologists as a diagnostic tool for personalizing patient care, as well as by researchers to accelerate and improve the process of drug discovery and development.

The collaboration will rely on the collective scientific, technical, clinical, and commercial expertise between the partners: MGH’s experience in clinical research and novel CTC technologies; the experience of Veridex as the only diagnostics company to have brought CTC technology to the U.S. market as an FDA-cleared in vitro diagnostic (IVD) assay ( “CellSearch® CTC Test”) for capturing and counting the number of tumor cells in the blood to help inform patients and their physicians about prognosis and overall survival in certain types of metastatic cancers; and ORD’s expertise in oncology therapeutics, biomarkers and companion diagnostics.  The platform to be developed will be a bench-top system to specifically isolate and explore the biology of rare cells at the protein, RNA and DNA levels.

“This new technology has the potential to facilitate an easy-to-administer, non-invasive blood test that would allow us to count tumor cells, and to characterize the biology of the cells,” said Robert McCormack, Head of Technology Innovation and Strategy, Veridex. “Harnessing the information contained in these cells in an in vitro clinical setting could enable tools to help select treatment and monitor how patients are responding.”

“The role of CTCs in drug discovery and development is growing as new technologies allow us to use CTCs for the first time as templates for novel DNA, RNA and protein biomarkers,” said Nicholas Dracopoli, Vice President, Biomarkers, ORD. “Given the demand for actionable data to guide personalized medicine for patients with cancer, there is a rapidly growing need for advanced, automated non-invasive technologies that can aid in selection of treatment and monitor response throughout the course of their disease.”

Mehmet Toner, Ph.D., Professor of Surgery, Massachusetts General Hospital (MGH) & Harvard Medical School; Director, MGH BioMicro- ElectroMechanical Systems Resource Center

“The challenging goal of sorting extremely rare circulating tumor cells from blood requires continuous technological, biological and clinical innovation to fully explore the utility of these precious cells in clinical oncology,” said Mehmet Toner, Ph.D., director of the BioMicroElectroMechanical Systems Resource Center in the MGH Center for Engineering in Medicine. “We have developed and continue to develop a broad range of technologies that are evolving what we know about cancer and cancer care. This collaboration is an opportunity to apply our past learning to the advancement of a platform that will ultimately benefit patients with cancer.”

Building on its successful development and evolution of CTC technology, as well as contributions to the body of science in the CTC field, MGH aims to revolutionize how oncologists detect, monitor and potentially treat cancers.  The MGH team has already developed two generations of a microfluidic chip capable of capturing CTCs with a high rate of efficiency. However the third generation technology now being developed with the companies is based on a new technological platform and will aim for even higher sensitivity, as well as suitability for broad applications and ready dissemination.

In the above demonstration of the first generation CTC-Chip, circulating tumor cells (fluorescent labeled, shown in white) mixed with blood (not labeled) are captured on nano-scale posts as they flow through the chip. The chip is the size of a microscope slide with 78,000 posts, which are coated with antibodies to epithelial cell adhesion molecules in tumor cells. (Video courtesy of Dr. Sunitha Nagrath, Massachusetts General Hospital/Harvard Medical School)

“This agreement is quite different from the usual academic-industrial agreement because we will be working together to bring new MGH-invented technology from its current, very early stage, through prototype and scale-up, to our ultimate goals of FDA approval and clinical adoption,” says Dr. Toner. “Our innovation team will be dedicated to developing this technology from its basic scientific principles all the way to initial prototyping within the biological research and clinical environments. Veridex has the knowledge required to translate early-stage technology into a product that can be reliably manufactured and meet regulatory requirements.

“Applying data gathered from CTCs to the care of cancer patients is a complex problem, and our strategy is to diversify technological approaches to find the best solutions for specific applications,” Toner adds. “We may find that different technologies work better for diagnosis, for prognosis and for the long-term goal of early detection; so we don’t want to confine ourselves to a single option.” His team is continuing to develop the microfluidic chip technology, with the support of Stand Up to Cancer.

Daniel A. Haber, M.D., Ph.D., Director, Massachusetts General Hospital Cancer Center

Daniel Haber, MD, PhD, director of the MGH Cancer Center, says, “The ability to establish a dedicated MGH research center focused on the intersection of bioengineering, molecular biology and clinical oncology presents an opportunity to develop a next-generation platform that will help us detect, define and monitor cancer cells more effectively – which should make an enormous difference in the lives of so many patients and their families.”

About Circulating Tumor Cells

Circulating tumor cells are cancer cells that have detached from the tumor and are found at extremely low levels in the bloodstream. The value of capturing and counting CTCs is evolving as more research data is gathered about the utility of these markers in monitoring disease progression and potentially guiding personalized cancer therapy.

About Veridex, LLC

Veridex, LLC, a Johnson & Johnson company, is an organization dedicated to providing physicians with high-value diagnostic oncology products. Veridex’s IVD products may significantly benefit patients by helping physicians make more informed decisions that enable better patient care. Veridex’s Clinical Research Solutions provide tools and services that may be used for the selection, identification and enumeration of targeted rare cells in peripheral blood for the identification of biomarkers, aiding scientists in their search for new, targeted therapies. For more information, visit www.veridex.com.

About Ortho Biotech Oncology Research & Development

Ortho Biotech Oncology Research & Development, a unit of Johnson & Johnson Pharmaceutical Research & Development, is a research and development organization that strives to transform cancer to a preventable, chronic or curable disease by delivering extraordinary and accessible diagnostic and therapeutic solutions that prolong and improve patients’ lives.

About Massachusetts General Hospital

Celebrating the 200th anniversary of its founding in 1811, Massachusetts General Hospital is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $600 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, systems biology, transplantation biology and photomedicine. For more information visit http://www.mgh.harvard.edu/.

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