Two decades beyond BRCA1/2: Homologous recombination, hereditary cancer risk and a target for ovarian cancer therapy

Abstract

Almost exactly 20 years after their discovery, the BRCA1 and BRCA2 genes have become the target of the first "personalized" therapy available for patients with ovarian cancer. In December 2014, a poly(ADP-ribose) polymerase (PARP) inhibitor was granted expedited approved by the United States Food and Drug Administration for use in advanced ovarian cancer patients with germline BRCA1/2 mutations who have received three or more prior lines of chemotherapy. This review article will discuss (1) the BRCA1 and BRCA2 genes within the larger context of homologous recombination deficiency; (2) the advances in our understanding of hereditary cancer risk and the dramatic shifts that have occurred in the genetic testing landscape since the landmark 2013 Supreme Court ruling invalidating patents on BRCA1 and BRCA2 genetic testing; and (3) the clinical trials leading to the approval of olaparib, the first in human PARP inhibitor.

Keywords: BRCA1; BRCA2; Genetic testing; Homologous recombination; PARP inhibitor synthetic lethality.