Emerging role of deubiquitinases in modulating cancer chemoresistance

Chemotherapy remains a gold standard in cancer treatment by targeting the rapidly dividing cancer cells. However, chemoresistance is a major obstacle to successful cancer treatment, often leading to recurrence, metastasis, and high mortality. Deubiquitinases (DUBs), enzymes that remove ubiquitin and stabilize proteins, have been implicated in chemoresistance and can either promote therapeutic resistance or enhance sensitivity depending on their targets. In this review, we highlight the chemoresistance mechanisms of DUBs in various cancers, including breast, lung, liver, gastrointestinal, colorectal, ovarian, prostate, and blood cancers. Given these mechanisms, the development of DUB inhibitors has gained considerable attention in cancer therapeutics and combination therapies involving these inhibitors show potential to overcome drug resistance and improving treatment outcomes.