BRCA1 and BRCA2 genes are tumor suppressor genes involved in DNA double-strand break repair via homologous recombination. Germline BRCA mutations significantly increase the lifetime risk of breast, ovarian, prostate, and pancreatic cancers.
PARP (poly ADP-ribose polymerase) inhibitors, such as olaparib and niraparib, exploit the concept of synthetic lethality: PARP inhibition in BRCA-deficient cells leads to accumulation of unrepaired DNA damage and selective cell death.
Olaparib is approved for germline BRCA-mutated HER2-negative metastatic breast cancer, ovarian cancer, fallopian tube cancer, primary peritoneal cancer, and pancreatic cancer. The use of PARP inhibitors has reshaped treatment paradigms in BRCA-associated cancers.