Integrating PARP Inhibitors Into Advanced Prostate Cancer Therapeutics.

DNA-damage repair (DDR) pathway mutations can sensitize cancer cells to a class of cancer therapeutics known as PARP inhibitors. Given that DDR alterations can be found in up to one-third of advanced prostate cancers, PARP inhibitors have recently been established in treatment-refractory settings. We provide an updated review of the clinical data supporting the 4 PARP inhibitors that have undergone the most investigation thus far in metastatic castrate-resistant prostate cancer (mCRPC). Two of these agents are currently approved for the treatment of DDR-altered mCRPC. We end with a discussion on integration of approved PARP inhibitors into advanced prostate cancer clinical practice.

Déclaration de conflit d'intérêts

ACKNOWLEDGMENT: This work was supported by grants from the Department of Defense (W81XWH-19-1-0388 to NAB and W81XWH-19-1-0406 to JG), the National Cancer Institute (CA233452 to NAB), and US Department of Veterans Affairs (BX001040 to NAB). FINANCIAL DISCLOSURE: JG—consultant to Amgen, Astellas, Elsevier, Exelixis, QED Therapeutics. EP—consultant to Bayer, Genentech/Roche, research funding Pfi zer. TD—consultant to Janssen, contracted research Merck. HS—stock and other ownership interests Radiogel, consultant to Janssen, other relationship to Caribou Publishing. MK—consultant to Augmenix, Varian Medical Systems. ZZ— contracted research Janssen. SJF—consultant to Janssen, Sanofi , Pfi zer, Astellas, Bayer, Dendreon, Merk, AstraZeneca. RF—consultant to Accelera, Bristol Myers Squibb, CBT Pharmaceuticals, Johnson & Johnson, Precision Health Economics. NB, HK, AG—nothing to disclose.