PARP Inhibitors Alone and in Combination with Other Biological Agents in Homologous Recombination Deficient Epithelial Ovarian Cancer: From the Basic Research to the Clinic

Hereditary epithelial ovarian cancer [EOC] in germline BRCA mutation (gBRCAm) carriers has a distinct clinical behavior characterized by younger age, high- grade serous histology, advanced stage, visceral distribution of disease, high response to platinum and other non-platinum agents and better clinical outcome. Sporadic EOC with homologous recombination deficiency [HDR] but no gBRCAm has the same biological and clinical behavior as EOC in gBRCAm carriers ("BRCAness"phenotype). Biomarkers are in development to enable an accurate definition of molecular features of BRCAness phenotype, and trials are warranted to determine whether such HDR signature will predict sensitivity to PARP inhibitors in sporadic EOC. Moreover, the link between PARP inhibition and angiogenesis suppression, the immunologic properties of EOC in gBRCAm carriers, the HRD induced by PI3K inhibition in EOC cells in vitro strongly support novel clinical trials testing the combination of PARP inhibitors with other biological agents.