Olaparib for the treatment of metastatic prostate cancer

Recent innovations in the treatment of metastatic prostate cancer have improved patient outcomes. Nonetheless, this disease remains fatal and additional treatment approaches are needed. Greater understanding of the molecular landscape of metastatic prostate cancer has revealed recurrent alterations in key pathways amenable to therapeutic targeting. One such pathway is DNA repair, particularly alterations in genes directly or indirectly associated with homologous recombination repair found in up to one-quarter of patients with metastatic castrate-resistant prostate cancer (mCRPC). Olaparib, an inhibitor of poly-ADP-ribose polymerase, has recently gained approval for the treatment of mCRPC harboring alterations in homologous recombination repair genes. This review will provide a summary of evidence regarding PARP inhibition in the treatment of mCRPC, with a specific focus on olaparib.Lay abstract The genetic material in cells, called DNA, is continually exposed to factors which can damage it. This damage must be corrected, which is done through specific DNA damage repair pathways. Mutations, which can be inheritable or arise just in the cancer itself, can occur in genes involved in DNA damage repair that impair the repair process. In 20–30% of prostate cancers, mutations are involved in genes associated with the homologous recombination repair pathway which can be taken advantage of for therapeutic effect by targeting an alternate repair pathway involving a protein called PARP. Olaparib, an inhibitor of PARP, was recently shown to improve outcomes in patients with advanced, metastatic prostate cancer harboring mutations in homologous recombination repair genes and subsequently gained approval for the treatment of such patients. This review will provide a summary of evidence regarding PARP inhibition in the treatment of prostate cancer, with a specific focus on olaparib.