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Cancers that develop in BRCA mutation carriers share a common trait: a defect in repairing a certain type of DNA damage. PARP inhibitors are a type of drug that exploit that defect by blocking the PARP enzyme that cells use to repair damaged DNA. Theoretically, these drugs should spare healthy cells that have at least one working copy of the BRCA gene, with limited side effects or toxicity. Some women with ovarian cancer who do not have BRCA mutations also respond to PARP inhibitors, probably because their cancers also have a decreased ability to repair DNA. A lot of effort is now being focused on developing biomarkers or tumor tests to identify signs of this diminished DNA repair ability in cancers, so that patients without BRCA mutations who are likely to respond to PARP inhibitors can be identified.
Early PARP inhibitor research generated lots of excitement. In initial trials, the well-tolerated drugs effectively treated some people with BRCA mutations and advanced cancers, including those who had already undergone multiple prior treatments with standard chemotherapy drugs.
In December 2014, the FDA approved the first PARP inhibitor, Lynparza (also known as olaparib), to treat ovarian, fallopian tube, and primary peritoneal cancer in women who carry mutations in BRCA1 or BRCA2, and who have completed three or more chemotherapy treatments.
Participation of the HBOC community in PARP inhibitor research is critical to expand the number of approved PARP inhibitors and develop treatments for different types of cancers. If you are interested in participating, ask your oncologist about studies in your area. Prior treatment sometimes affects participation eligibility; if you are newly diagnosed with a primary or recurring cancer, consider enrolling in a PARP inhibitor trial as early after diagnosis as possible. Share this information with friends and relatives.