The SUMO pathway in pancreatic cancer: insights and inhibition

Abstract

An urgent medical need to develop novel treatment strategies for patients with pancreatic ductal adenocarcinoma (PDAC) exists. However, despite various efforts in the histopathological and molecular subtyping of PDAC, novel targeted or specific therapies have not been established. Posttranslational modifications (PTMs) with ubiquitin-like proteins, including small ubiquitin-like modifiers (SUMOs), mediate numerous processes that can contribute to the fitness and survival of cancer cells. The contribution of SUMOylation to transcriptional control, DNA repair pathways, mitotic progression, and oncogenic signalling has been described. Here we review functions of the SUMO pathway in PDAC, with a special focus on its connection to an aggressive subtype of the disease characterised by high MYC activity, and discuss SUMOylation inhibitors under development for precise PDAC therapies.