A Comprehensive Review on PARP Inhibitors in Targeted Therapy for Cancers

The poly (ADP-ribose) polymerase (PARP) family of enzymes involves and regulates various cellular processes and essential functions, such as apoptosis, transcription process, and DNA repair. PARPs (PARP-1, PARP-2, PARP-3) are a branch of familiar proteins that play a crucial role in repairing DNA damage in a human gene involved in different cancers and regulate the base excision repair (BER) pathway. As a target-based drug therapy for cancer, inhibition of PARP stops the PARP-1 and -2 from repairing damaged and mutated DNA in cancer cells, and eventually, the cancer cells die. Considering the limited available therapies for the treatment of advanced and recurrent cancers, PARP inhibitors (PARPi) are the first approved cancer drugs that particularly target the response to DNA damage in BRCA (BReast CAncer gene)-1/2 mutated ovarian, pancreatic, prostate, and breast cancers. Recently, six PARPi viz., olaparib, rucaparib, niraparib, talazoparib, fuzuloparib, and pamiparib were approved as monotherapy or in combination with other classes of anticancer agents for the maintenance treatment of advanced or recurrent cancers. Moreover, PARPi appears to improve progression-free survival in women with recurrent platinum-sensitive ovarian cancer as an adjuvant to the conventional treatment. Importantly, the use of PARPi in the management of germline BRCA1/2-associated cancers is a novel therapeutic strategy, representing the first successful targeted therapy in improving outcomes in patients with hereditary cancers. Although resistance to these agents has been reported recently, however, various therapeutic strategies have been employed to overcome resistance and improve the sensitivity of PARPi in the treatment of ovarian, breast, gastric, pancreatic, and prostate cancers.