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May 8, 2019

Why do ovarian cancer drugs work for some patients but not others?

A new class of drugs called PARP inhibitors has successfully slowed the spread of ovarian cancer for some patients, but the treatments are less effective for many others.

"That's always been a question, why some patients don’t respond to treatments as well as others," said Jose Teixera, a professor in the MSU College of Human Medicine’s department of obstetrics, gynecology and reproductive biology.

With a $50,000 grant awarded by the Michigan Ovarian Cancer Alliance today – World Ovarian Cancer Day – Teixeira and John Risinger, a professor of obstetrics, gynecology and reproductive biology and the college’s director of gynecologic oncology research, hope to find out why many ovarian cancer patients do not respond well to PARP inhibitors. The answer, they believe, can be found in a cellular protein called PTEN.

Normally, the PTEN gene is a tumor suppressor that, when mutated, can drive the development of many types of cancer, including of the ovaries. Teixeira and Risinger hypothesize that if PTEN is in the nuclei of the cancer cells, the PARP inhibitor treatment is less effective. The two researchers have found PTEN in the nuclei of more than half of the ovarian cancer cells they have studied, which they believe might explain why a majority of patients don’t respond well to PARP inhibitors.

Ovarian cancer is difficult to detect in its early stages and usually is not diagnosed until after it has spread to other organs, making it more resistant to treatment. Ovarian cancer ranks fifth in cancer deaths among women and accounts for more deaths than any other cancer of the female reproductive system.

The Michigan Ovarian Cancer Alliance grant will allow Teixeira and Risinger to test their hypothesis and gather enough data to apply for a larger National Institutes of Health grant. That, in turn, would allow them to conduct a more in-depth study of which patients are likely to respond well to PARP inhibitors, as well as which ones are not.

“We’re delighted that we have received this grant from the Michigan Ovarian Cancer Alliance,” Teixeira said. “It will allow us to pursue this theory, which will, hopefully, lead to better, more patient-specific treatments for ovarian cancer patients.”

Risinger said he is “really excited about this work and its potential to help ovarian cancer patients”, and that this grant will help with the move forward in the studies.

The U.S. Food and Drug Administration has approved several drugs in the PARP inhibitor class for treating ovarian cancer in patients who have mutations in the BRCA genes. But BRCA mutations are found in only about five percent of ovarian cancer patients, which is why Teixeira and Risinger plan to broaden their research beyond only those patients.

“We want to open it up to more of those [ovarian cancer] patients who don’t have a BRCA mutation,” Teixeira said.

By: Geri Kelley