The Role of PARP Inhibitors in Ovarian Cancer

Michael Birrer, MD, PhD, professor of medicine, Harvard Medical School, director, Gillette Center for Gynecologic Oncology, Massachusetts General Hospital, discusses the role of PARP inhibitors in ovarian cancer.

Birrer says there is a lot of interesting science going on in the clinical research of ovarian cancer but PARP inhibition is the most mature. Birrer believes that a PARP inhibitor could be approved within the next two years.

PARP inhibitors were developed with elaborate laboratory work that showed that PARP is a protein that repairs single strand breaks in DNA, Birrer says. PARP inhibition is critical in cells that are missing BRCA1 or BRCA2. Inhibiting PARP in those cells causes double-strand DNA breaks, Birrer says, which causes synthetic lethality.

Although PARP inhibitors worked well in a laboratory setting and transitioned well into a clinical setting, Birrer says, there were some drug development mistakes that kept shifting the endpoints and some pharmaceutical companies put a stop on the development of PARP inhibitors. However, this has changed in the last two years and at least three major companies are progressing towards randomized phase III registration trials using PARP inhibitors in ovarian cancer.

Clinical Pearls

• PARP inhibitors may be approved within the next two years
• PARP inhibitors cause synthetic lethality in tumor cells of patients who have mutations inBRCA1orBRCA2
• The development of PARP inhibitors were stopped briefly but there are now 3 major companies that are rushing towards randomized phase III registration trials using PARP inhibitors in ovarian cancer