Oon, C. E., Anbazhagan, P., & Tan, C. T. (2025). Therapeutic potential of targeting ubiquitin-specific proteases in colorectal cancer. Drug Discovery Today, 30(5), 104356. https://doi.org/10.1016/j.drudis.2025.104356
Abstract:
Ubiquitin-specific proteases (USPs) are a subset of deubiquitinating enzymes (DUBs) that have crucial roles in regulating key signaling pathways, DNA repair mechanisms, and immune responses by modulating the interactions and stability of proteins, including oncogenes and tumor suppressors in many cancers, such as colorectal cancer (CRC). USPs present an attractive reservoir of drug targets that could potentially overcome the shortcomings of conventional pathway-specific cancer therapies. This review explores the roles of USPs in CRC, addresses the challenges in discovering and developing USP inhibitors, highlights recent advancements in drug development, and discusses the potential of targeted protein degraders and stabilizers including proteolysis-targeting chimeras (PROTACs), molecular glues, and DUB-targeting chimeras (DUBTACs) as strategies for drugging USPs.
License type:
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Funding Info:
This research / project is supported by the Singapore National Academy of Science, National Research Foundation - RIE2025 NRF International Partnership Funding Initiative
Grant Reference no. : N. A.
This research is supported by core funding from: Experimental Drug Development Centre
Grant Reference no. : N. A.