Exploiting DNA damage response protein O-glycosylation to enhance chemotherapy in pancreatic cancer.

Pancreatic cancer (PC) is the fourth leading cause of cancer deaths [1]. Presently, chemotherapy based on gemcitabine (GEM) is one of the most widely used schemes for PC, but this standard approach appears poorly effective in patients due to resistance development [2]. GEM-resistance is related to cancer metabolism rewiring. Noteworthy, PC exhibits an increased flux through the Hexosamine Biosynthetic Pathway (HBP), involved in protein glycosylation. Recently, it has emerged that HBP regulates DNA damage response, activating DNA Damage Repair (DDR) mechanisms [3]. The project aims to delineate if HBP inhibition and protein O-glycosylation impact on pancreatic cancer chemotherapeutics resistance.