New Therapeutic Options for BRCA Mutant Patients.

Abstract

Pathogenic variants in <i>BRCA1</i> and <i>BRCA2</i> are associated with significantly elevated lifetime risks of breast, ovarian, pancreatic, and prostate cancer. These genes are critical in double-strand break repair through homologous recombination. An understanding of the biology of <i>BRCA1</i> and <i>BRCA2</i> led to the development of targeted therapeutics, specifically poly(ADP-ribose) polymerase (PARP) inhibitors, which are approved by the US Food and Drug Administration for multiple <i>BRCA1/2</i>-associated cancers. Here, we discuss the development of PARP inhibitors, mechanisms of resistance, and the potential utility of these drugs beyond canonical <i>BRCA1/2</i> tumors, and we describe novel agents under study.