Therapeutic Potential of Targeting Transforming Growth Factor-beta (TGF-β) and Programmed Death-ligand 1 (PD-L1) in Pancreatic Cancer

Abstract: Pancreatic cancer (PC) is one the most lethal malignancies worldwide affecting around half a million individuals each year. The treatment of PC is relatively difficult due to the difficulty in making an early diagnosis. Transforming growth factor-beta (TGF-β) is a multifunctional factor acting as both a tumor promoter in early cancer stages and a tumor suppressor in advanced disease. Programmed death-ligand 1 (PD-L1) is a ligand of programmed death-1 (PD-1), an immune checkpoint receptor, allowing tumor cells to avoid elimination by immune cells. Recently, targeting the TGF-β signaling and PD-L1 pathways has emerged as a strategy for cancer therapy. In this review, we have summarized the current knowledge regarding these pathways and their contribution to tumor development with a focus on PC. Moreover, we have reviewed the role of TGF-β and PD-L1 blockade in the treatment of various cancer types, including PC, and discussed the clinical trials evaluating TGF-β and PD-L1 antagonists in PC patients.