The Poly(ADP-ribose) polymerase inhibitors in pancreatic cancer

Abstract

Genome instability and mutations are the hallmarks of cancer. Mutations within BRCA genes increase the risk of pancreatic cancer (PC) development. Poly(ADP-ribose) polymerase inhibitors (PARPi) show the synthetic lethality phenomenon in tumoral cells with BRCA mutation and improve outcomes in patients with breast, prostate and ovarian cancer. Olaparib was the first PARPi registered for the patient with metastatic PC with a deleterious or suspected deleterious germline BRCA-mutation. The POLO phase III clinical trial shows that olaparib in PC increases progression-free survival, however it does not prolong the overall survival. Currently, many clinical trials are ongoing to determine the clinical utility of PARPi in monotherapy or polytherapy of PC. The role of PARPi in PC has not been well established and many questions remain unanswered. This review aims to summarise the rationales behind the use of PARPi and current clinical data.