Dr. McCann on Resistance Mutations in Ovarian Cancer

Kelly McCann, MD, PhD, a medical oncologist in the Breast Cancer Research Group at the University of California, Los Angeles, discusses resistance mutations in ovarian cancer.

Physicians know that patients with germline BRCA1/2 mutations can get reversion mutations, regain the ability to perform homologous recombination and become resistant to PARP inhibitors. That is 1 mechanism of resistance, but there are other mechanisms of resistance that have been identified, explains McCann such as efflux pumps that pump the drug back out of the cell.

There is some interest in using PI3K inhibitors in these patients because activation of and increased signaling in that pathway may contribute to PARP inhibitor resistance, says McCann. PI3K is activated in many cancers because cell proliferation is increased. It may also be involved in angiogenic pathways, McCann adds.

Therefore, many clinical trials are trying to use PARP inhibitors and target the PI3K pathway simultaneously, so that they can be used longer in the patients who benefit from the treatment, states McCann.