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Pathogenic variants in BRCA1 and BRCA2 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 BRCA1 and BRCA2 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 BRCA1/2 -associated cancers. Here, we discuss the development of PARP inhibitors, mechanisms of resistance, and the potential utility of these drugs beyond canonical BRCA1/2 tumors, and we describe novel agents under study.
Ghanem et al. (2024) studied this question.