The new understanding of the importance of HR deficiency has important implications for the design of clinical trials. At present many trials of potential new treatments for ovarian cancer restrict enrollment to patients with high-grade serous disease. It’s now clear that such restrictions exclude many patients who could benefit from drugs with activity in the setting of HR deficiency, Dr. Zorn said.
Homologous recombination deficiency increases tumor sensitivity to a variety of medications, including platinum, pegylated liposomal doxorubicin, antiangiogenic agents, and PARP inhibitors, she added.
The 16 HR genes Dr. Norquist scrutinized in GOG 218 are BRCA1/2, BRIP1, PALB2, RAD51C, RAD51D, ATM, ATR, NBN, SLX4, BARD1, BLM, CHEK2, RBBP8, MRE11A, and XRCC2. These genes lie along what has come to be called the Fanconi Anemia/BRCA homologous recombination pathway.