Homologous recombination deficiency in ovarian cancer and beyond

Abstract

It has been well established that failure in the homologous recombination repair (HRR) mechanism for DNA double strand repair causes genomic instability and increases the risk for cell transformation. Mutations in BRCA1 and BRCA2 are currently known to be the most frequent responsible for homologous recombination deficiency (HRD) but HRD can occur through other processes including mutations and epigenetic aberration of HRD-related genes and the indirect interaction of BRCA proteins with other proteins involved in the DNA repair. Current efforts in this field are concentrating in identifying an HRD molecular signature able to predict response to chemotherapy and PARP inhibitors, thus allowing to extend novel targeted treatments beyond germline BRCA mutated ovarian cancer patients. The aim of this brief review is to summarize the current evidence regarding HRD beyond germline BRCA mutations and therapeutic approaches.