Tag Archives: Oncogene

“Shielded” Ovarian Cancer Cells May Survive Chemotherapy

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Cancer Research UK scientists have discovered certain ovarian tumor cells that are resistant to chemotherapy can survive a first round of treatment and go on to “re-grow” the cancer.

Cancer Research UK scientists have discovered certain ovarian tumor cells that are resistant to chemotherapy can survive a first round of treatment and go on to “re-grow” the cancer. This could help explain why the disease can be difficult to treat, according to new research published in Oncogene on June 28.

The study, funded by Cancer Research UK, aimed to find out whether it is the chemotherapy itself that causes anti-cancer drug resistance to build in the body – similar to resistance to antibiotics – or if cells that are shielded against cancer treatment grow as part of the initial tumor and are already lying dormant before chemotherapy begins.

Often ovarian cancer can be hard to treat with treatment failing after women initially responded well. The number of women surviving beyond five years is less than 35 per cent.

The researchers compared the characteristics of cell lines from the tumor at the time of diagnosis to cell lines from the same patients once the disease had been treated and become resistant.

Dr. James Brenton, Researcher, Functional Genomics of Ovarian Cancer, Cambridge Research Institute

Dr. James Brenton, study author from the Cancer Research UK’s Cambridge Research Institute, said:

“Ovarian cancer is notoriously hard to treat. Women usually respond well to their first round of chemotherapy with the disease apparently completely removed.  But unfortunately many go on to relapse within six to 24 months. Until now we haven’t known whether they are becoming resistant to the treatment or whether the cells that don’t respond to treatment re-grow the tumour.

By examining the characteristics of ovarian tumours we now think that cells resistant to chemotherapy grow as part of the tumor. This means that when patients have treatment, cells that respond to chemotherapy are destroyed but this leaves behind resistant cells which then form another tumor of completely resistant cells. This seems to explain why successful treatment for relapsed patients is difficult. What needs to be developed now is a therapy designed to target the resistant cells.”

Dr. Lesley Walker, director of science information at Cancer Research UK, said:

“Discoveries like this help to tell us why chemotherapy stops working for some ovarian cancer patients. We hope it will lead to new ways to tackle the disease and increase the number of women that survive this cancer that can be so hard to cure. The next step will be to develop treatment tailored to fight the resistant cells.”

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Disarming Specialized Stem Cells Might Combat Ovarian Cancer

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Eliminating cancer stem cells (CSCs) within a tumor could hold the key to successful treatments for ovarian cancer, which has been notoriously difficult to detect and treat, according to new findings published this week in the journal Oncogene by Yale School of Medicine researchers.

Eliminating cancer stem cells (CSCs) within a tumor could hold the key to successful treatments for ovarian cancer, which has been notoriously difficult to detect and treat, according to new findings published this week in the journal Oncogene by Yale School of Medicine researchers.

“We found that stopping the expression of two genes—Lin28 and Oct4—reduces ovarian cancer cell growth and survival,” said Yingqun Huang, M.D., Ph.D., assistant professor in the Department of Obstetrics, Gynecology & Reproductive Sciences at Yale School of Medicine.

Ovarian cancer is challenging to treat because it tends to recur frequently and develop resistance to treatment. The poor outcome for women with ovarian cancer is associated with subtle and nonspecific symptoms—earning it the moniker the “disease that whispers.”

“This recurrence and drug resistance may be due to the presence of CSCs within the tumors that have the capacity to reproduce and to differentiate into non-CSC tumor cells that repopulate the tumor mass,” said Huang, who is a member of Yale Stem Cell Center and Yale Cancer Center. “Eliminating these CSCs may be key to successful treatments.”

While in the process of studying the functions of stem cell proteins in human embryonic stem cells, Huang and her colleagues unexpectedly discovered that a sub-population of ovarian cancer cells express stem cell proteins Lin28 and Oct4. They also found that the two proteins appear to act together in ovarian cancer tissue cells to produce more advanced tumors. Inhibiting their combined expression led to a significant decrease in the growth and survival of cancer cells. A larger-scale ovarian cancer study is currently underway to confirm the significance of the findings.

Genetic researchers prevent genes from functioning — a process commonly referred to as “knocking down” the gene — by inserting small interfering RNA (siRNA) molecules into the cells. Next, the research team will examine the effect of siRNA in ovarian cancer cells in the lab, and test the technique on mice. If successful, human clinical trials would follow. Treatment on cancer patients could occur within 10 years, Huang said.

“We hope we will soon be able to apply this new information to improve outcomes, perhaps by developing better diagnostic markers and treatment strategies that may be useful in customizing treatment for ovarian cancer patients,” said Huang.

The study was supported by Connecticut Innovations, the Fannie E. Rippel Foundation and the National Cancer Institute.

Other Yale authors on the study included Nita Maihle, Ph.D., and Shuping Peng.

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