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Poly(ADP-ribose) polymerase inhibitors in breast cancer and other tumors: advances and challenges

Mustafa Khasraw, Mark Robson

Poly(ADP-ribose) polymerase (PARP) inhibitors are currently in development for the treatment of cancer. PARP-1 and PARP-2 are important in the repair of DNA damage. PARP inhibitors used either as single agents or in combination with other cytotoxics, aim to increase efficacy of DNA damage. When PARP is inactivated in cells lacking functional BRCA1 or BRCA2, cells reach a high degree of genomic instability and die. Populations studied in ongoing and reported clinical trials include BRCA mutation-associated cancers, as well as sporadic breast cancers, ovarian cancers and other malignancies. In this review, PARP inhibitors undergoing clinical trial evaluation in humans (olaparib, iniparib, veliparib, rucaparib, MK-4827 and INO-1001) are discussed, with a focus on breast cancer, but also other tumors and the recently reported study results.