Researchers at Michigan State University (MSU) were granted $50,000 to investigate why only a fraction of ovarian cancer patients respond to treatment with PARP inhibitors.
The grant, awarded by the Michigan Ovarian Cancer Alliance, will allow the team to better understand the biological mechanisms underlying patients’ response to PARP inhibitors, or lack thereof.
Data collected from the studies are expected to support submission of an application for a larger grant from the National Institutes of Health.
“We’re delighted that we have received this grant from the Michigan Ovarian Cancer Alliance,” Jose Teixeira, a professor at the MSU College of Human Medicine’s department of obstetrics, gynecology, and reproductive biology, said in a press release. “It will allow us to pursue this theory, which will, hopefully, lead to better, more patient-specific treatments for ovarian cancer patients.”
As cancer cells divide at a faster pace, they are prone to accumulating more errors in their genome than healthy cells. To avoid these genetic mistakes, cells have a specific machinery dedicated to finding these errors and correcting them, holding off additional cellular damage.
Among the critical components of this corrective mechanism are PARP enzymes, without which cells are unable to correct these cumulative genetic errors.
Taking advantage of this process, researchers have developed specific PARP inhibitors to promote cancer cells’ death.
Lynparza (olaparib), an oral inhibitor of PARP, was approved in 2014 as a maintenance therapy for women with platinum-sensitive relapsed ovarian cancer and BRCA mutations, but recent data supporting its effectiveness in women without BRCA mutations led to its approval regardless of BRCA status.
Besides Lynparza, two other PARP inhibitors — Zejula (niraparib), developed by Tesaro, and Clovis Oncology’s Rubraca (rucaparib) — have been approved as maintenance therapy for women with advanced, relapsed ovarian cancer who are in complete or partial response to platinum-based chemotherapy.
These therapies are particularly effective in cancers with mutations in other DNA-repairing genes, such as BRCA1 and BRCA2. However, only 5.8% to 24.8% of all ovarian cancer patients carry BRCA mutations, and many patients fail to respond effectively to PARP inhibitors.
Researchers believe that a gene called PTEN could be responsible for this reduced responsiveness to PARP inhibitors in some ovarian cancer patients.
“That’s always been a question, why some patients don’t respond to treatments as well as others,” Teixeira said.
PTEN is a tumor suppressor that when in the nucleus favors genomic stability and restrains cell cycle progression. But when this gene is mutated, it can also drive the development of several cancer types, including ovarian cancer.
In previous studies, MSU researchers found that PTEN is located in the cell’s nucleus in over half of the ovarian cancer patients they have evaluated. Based on these findings, the team believes that PTEN could hold an answer as to why many patients do not respond to PARP inhibitors.
The other lead investigator, John Risinger, a professor of obstetrics, gynecology, and reproductive biology at MSU, said he is “really excited about this work and its potential to help ovarian cancer patients,” which might open the possibility of using PARP inhibitors with “more of those [ovarian cancer] patients who don’t have a BRCA mutation.”
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