Two decades beyond BRCA1/2: Homologous recombination, hereditary cancer risk and a target for ovarian cancer therapy.
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.
Department of Obstetrics and Gynecology, Cedars-Sinai Medical Center, Los Angeles, CA, USA. Electronic address: walshc@cshs.org.
Christine S
CS
Walsh
D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D045744:Cell Line, Tumor; D005260:Female; D005820:Genetic Testing / Q000379:methods*; D059765:Homologous Recombination; D006801:Humans; D058990:Molecular Targeted Therapy; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*
D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human
BRCA1; BRCA2; Genetic testing; Homologous recombination; PARP inhibitor synthetic lethality