Dr. Konecny on Resistance to PARP Inhibitors in Ovarian Cancer

Gottfried E. Konecny, MD, associate professor of medicine, University of California, Los Angeles, discusses resistance to PARP inhibitors in ovarian cancer.

Resistance is a complex issue, but physicians have begun to understand that prior exposure to chemotherapy decreases a patient’s potential response to PARP inhibitors. Konecny states that this could be a result of genetic adaptions to the therapy, which are known as reversion mutations. These are genetic changes that happen during treatment or during the preceding platinum treatment that restore a normal or partially normal BRCA protein. These new mutations restore the DNA repair deficiency and weaken the efficacy of PARP inhibitors.

Further research has demonstrated that escape mechanisms are another means of treatment failure. Physicians are trying to avoid these mechanisms by developing trials that will look at combination therapies with PARP inhibitors. These include antiangiogenic agents and the class of immuno-oncology drugs that include drugs such as MEK inhibitors or DNA-damaging agents that may augment or synergize with PARP inhibition. These include ATM and WEE1 inhibitors, says Konecny.