OTU deubiquitinases in cancer pathogenesis and precision therapy

The OTU family consists of 16 highly conserved deubiquitinases (DUBs) that play critical roles in regulating diverse signaling pathways through substrate-specific deubiquitination of key proteins. These enzymes are involved in multiple physiological processes, including cancer progression, immune responses, cell division, and inflammation modulation. Depending on their target substrates, individual OTU family members perform distinct functions across biological processes, as exemplified by their dual roles in cancer pathogenesis. Increasing attention has been directed toward developing OTU DUB inhibitors as potential cancer therapeutics. This review provides a systematic analysis of recent structural and functional studies on OTU family members, with a particular focus on their roles in cancer. We discuss their associations with various malignancies and summarize advances in OTU-targeted inhibitor development, emphasizing their clinical potential as novel therapeutic targets.