By Admin at 9 Dec 2015, 14:03 PM

One of the main hurdles to increasing outcomes among ovarian cancer patients is resistance to chemotherapy. It’s estimated that 75 percent of women with advanced ovarian cancer initially respond to chemotherapy treatment, but the majority will relapse within two years.

When relapse occurs, subsequent courses of chemotherapy may prove to be ineffective, especially if the relapse occurred within six months of completing the initial treatment. The other 25 percent of women with advanced ovarian cancer tend to be cases that do not respond to chemotherapy at all.

If researchers could pinpoint the underlying mechanisms causing chemoresistance, it could lead to significantly better treatments and survival rates. University of Georgia (UGA) College of Pharmacy associate professor Shelley Hooks stated in Medical Xpress:

“Chemoresistance to ovarian cancer is what kills women … It's the deadliest gynecologic cancer. Most women with ovarian cancer will have their tumors come back."

Over the last five years, Hooks and colleagues have made major strides in this area. Their research, published in the journal Future Medicinal Chemistry, revealed that the RGS10 protein impacts the effectiveness of chemotherapy for ovarian cancer.

The effects of RGS10, in turn, are driven by mTOR signaling, which is a protein encoded by the mTOR gene. MTOR plays a role in determining whether or not cells survive, which is how it likely influences chemotherapy’s effectiveness. Researchers described RGS10 as an “off switch” that leaves a person resistant to chemotherapy.

When they tested whether ovarian cancer cells would be affected by common chemotherapy drugs, they were able to make the drugs either more or less effective by altering RGS10 expression. Interestingly, RGS10 could be turned off epigenetically, meaning due to environmental factors as opposed to genetic ones.

Further research on mTOR inhibitors could one day lead to significantly better ovarian cancer treatments. UGA College of Pharmacy associate professor Mandi Murph, who also worked on the study, told Medical Xpress:

“Within two years, 85 percent of women will have their cancer come back in a more aggressive form … It is during that time that they won't respond to the chemotherapy … Chemoresistance prevents us from curing the disease … If we can cure chemoresistance, we can cure ovarian cancer."

Ovarian cancer is the fifth deadliest cancer among U.S. women. While rates of ovarian cancer have been falling over the last two decades, about one in 75 women will develop ovarian cancer during her lifetime and, currently, one in 100 will die of the disease.

Sources:
Future Medicinal Chemistry August 2015
Medical Xpress October 26, 2015
Medscape Future Oncology

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