Journal Article

The SUMO pathway in pancreatic cancer: insights and inhibition

Schick, Markus, Schneeweis, Christian, Schneider, Günter, Keller, Ulrich, Hassan, Zonera

2021

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/67/1059/602 / 692/4028/67/1059/602 / Adenocarcinoma / Biomedical and Life Sciences / Biomedicine / Cancer Research / Cancer therapies / Carcinoma, Pancreatic Ductal - metabolism / Carcinoma, Pancreatic Ductal - pathology / Cell Survival - physiology / Chemotherapy / Cysteine Endopeptidases - drug effects / Cysteine Endopeptidases - metabolism / DNA damage / DNA repair / DNA Repair - physiology / Drug Resistance / Enzyme Inhibitors - pharmacology / Enzymes / Epidemiology / Growth factors / Humans / Hypoxia / Leukemia / Localization / Medical prognosis / Medical research / Metastasis / Mitosis - physiology / Molecular Medicine / Myc protein / Oncology / Pancreatic cancer / Pancreatic Neoplasms - metabolism / Pancreatic Neoplasms - pathology / Patients / Poly-ADP-Ribose Binding Proteins - metabolism / Promyelocytic Leukemia Protein - metabolism / Protein Inhibitors of Activated STAT - metabolism / Protein Processing, Post-Translational / Proteins / Proto-Oncogene Proteins c-myc - genetics / Proto-Oncogene Proteins c-myc - metabolism / Review / Review Article / Signal transduction / Signal Transduction - physiology / Small Ubiquitin-Related Modifier Proteins - antagonists & inhibitors / Small Ubiquitin-Related Modifier Proteins - metabolism / SUMO protein / SUMO-1 Protein - antagonists & inhibitors / SUMO-1 Protein - metabolism / Sumoylation - drug effects / Synthetic Lethal Mutations / Transcription / Ubiquitin / Ubiquitin-Conjugating Enzymes - antagonists & inhibitors / Ubiquitin-Conjugating Enzymes - metabolism / Ubiquitins - antagonists & inhibitors / Ubiquitins - metabolism