Treatment with onvansertib, a specific PLK1 inhibitor, overcomes olaparib resistance in high-grade serous ovarian carcinoma patient-derived xenografts

Inhibitors of PARP (PARPis) represent the first clinically approved anticancer agents targeting the DNA damage response. They have been approved as monotherapy and/or in combination and maintenance settings in different tumor types, including high-grade ovarian carcinomas. Their efficacy was first underlined in cells with functional inactivation of BRCA1 and BRCA2 genes and this strong preclinical evidence prompted their clinical development in tumors with BRCA1/BRCA2 mutations. It was later demonstrated that PARPis were very effective in tumors displaying deficiency in homologous recombination (HR) repair beyond BRCA1 and BRCA2 loss of function. In addition, evidence from randomized clinical trials supports their efficacy also in tumors with intact HR repair, although to a lesser extent.