As part of an ongoing series of answers to common questions received by the Basser Center for BRCA, Executive Director Susan Domchek, MD, discusses PARP inhibitors and ways in which they might be combined with other cancer treatments.

Dr. Domchek: So the good news is that we have made progress in therapies directed specifically at BRCA1 and BRCA2 mutations. The drugs that were initially approved are called PARP inhibitors and they've been approved for BRCA1/2-related ovarian cancer and BRCA1/2 mutation-associated breast cancer. We anticipate that there will also be approval soon for BRCA1/2-related pancreatic cancer [which just happened very recently!]. All of these drugs have been a great advancement.

But they're not good enough and the vast majority of the time the tumors learn to become resistant to these PARP inhibitors.
So the question, of course, is how can we make these PARP inhibitors better? There's a lot of interest in combining PARP
inhibitors with other medications. It's actually difficult to combine PARP inhibitors with chemotherapy, because both chemotherapy
and PARP inhibitors can make blood counts go down, so we have to be very careful about what kinds of chemotherapy to try to combine it with and how to do that.

There's a lot more interest in combing PARP inhibitors with other what we call small molecule or targeted therapies - meaning targeting other DNA repair pathways. There are drugs, for instance, such as ATR inhibitors, that are in clinical trials in combination with PARP inhibitors and we hope that that will both increase response rates, but also decrease the development of resistance in tumors. Another general approach is to combine PARP inhibitors with immune therapies to see whether or not we can make the responses that occur
with PARP inhibitors longer and more durable. Right now it's really important that people enroll in clinical trials so we can figure out what the best combinations are and for which patients.