DNA damage response and repair in pancreatic cancer development and therapy

Pancreatic cancer (PC) is among fatal malignancies, with a dismal prognosis and a low survival rate of 5-10%. In both sporadic and inherited PC, gene alterations, such as BRCA1/2, PALB2, and ATM, can occur frequently. Currently, surgery, chemo- and radio-therapy are the most common therapeutic strategies for treating this cancer. DNA damage response (DDR) establishes multiple pathways that eliminate DNA damage sites to maintain genomic integrity. Various types of cancers and age-related diseases are associated with DDR machinery defects. According to the severity of the damage, DDR pathways respond appropriately to lesions through repairing damage, arresting the cell cycle, or apoptosis. Recently, novel agents, particularly those targeting DDR pathways, are being utilized to improve the response of many cancers to chemotherapy and radiotherapy. In this paper, we briefly reviewed DDR processes and their components, including DDR sensors, DDR mediators, and DDR transducers in the progression, prognosis, and treatment of PC.