USP13: A therapeutic target for combating tumorigenesis and antitumor therapy resistance

Ubiquitin-specific peptidase 13 (USP13) has emerged as a key regulator of proteins critical to the hallmarks of cancer, playing an essential role in cellular regulation. This deubiquitinating enzyme, often overexpressed in malignancies, wields its molecular scissors precisely, snipping ubiquitin tags to rescue oncoproteins from degradation. Our review highlights the dual role of USP13 in cancer biology: while it predominantly fuels tumor growth and metastasis, USP13 occasionally functions as a tumor suppressor. USP13 is as a formidable factor in cancer therapy, fortifying tumors against an arsenal of treatments. It bolsters DNA repair mechanisms, ignites prosurvival autophagy, and even reprograms cell lineages to evade targeted therapies. However, USP13 is also a promising target in the treatment of cancer. We highlight burgeoning strategies to neutralize USP13, from small molecule inhibitors to innovative protein degraders, which may disarm cancer resistance mechanisms. We also offer suggestions for future USP13 research, emphasizing the need for structural insights and more potent inhibitors. This review highlights the critical role of USP13 in cancer and underscores its potential as a therapeutic target for advancing cancer treatment.