Subset of Ovarian Cancer Cells Are CA125-Negative and Resistant to Platinum Therapy; Birinapant Drug Sensitizes These CA125-Negative Cells to Platinum; Platinum/Birinapant Combination May Address 85% Recurrence Rate in Ovarian Cancer

High-grade serous ovarian cancer often responds well to the chemotherapy drug carboplatin, but why it so frequently comes back after treatment has been a medical mystery. Now a team of UCLA researchers has discovered that a subset of tumor cells that don’t produce the protein CA125, a biomarker used to test for ovarian cancer, has an enhanced ability to repair their DNA and resist programmed cell death — which allows the cells to evade the drug and live long enough to regrow the original tumor. It’s that regenerative ability and their resistance to carboplatin therapy that make the cells so dangerous, said Dr. Deanna Janzen, the study’s first author, and a Senior Scientist in the G.O. Discovery Lab at UCLA. The study, which appeared online on August 3, 2015 in an open-access article in Nature Communications, showed that pairing the carboplatin chemotherapy with an experimental drug eliminates the deadly population of cells believed to be responsible for repopulating the tumor. The additional drug, birinapant, sensitizes the CA125-negative cells to the chemotherapy by restoring apoptosis, or programmed cell death, said Dr. Sanaz Memarzadeh (photo), a senior author of the study and a UCLA gynecologic cancer surgeon. The open-access Nature Communications article is titled “An Apoptosis-Enhancing Drug Overcomes Platinum Resistance in a Tumour-Initiating Subpopulation of Ovarian Cancer.” Combining chemotherapy and birinapant significantly improved disease-free survival in laboratory models of human ovarian cancer compared to using either therapy alone. This suggests that targeting the CA125-negative cells may improve outcomes in these high-grade serous cancers, the most common subtype of ovarian cancer, said Dr.
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