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Progress in RAS-targeted therapeutic strategies: From small molecule inhibitors to proteolysis targeting chimeras

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MEDICINAL RESEARCH REVIEWS
卷 -, 期 -, 页码 -

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WILEY
DOI: 10.1002/med.21993

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cancer; drug resistance; mutation; PROTAC; RAS

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This review discusses the critical role of RAS gene mutations in fatal cancers and explores the potential of PROTAC strategy as a powerful tool for handling undruggable targets. PROTAC is expected to become a feasible strategy to overcome the bottleneck of classical RAS inhibitors.
As a widely considerable target in chemical biology and pharmacological research, rat sarcoma (RAS) gene mutations play a critical driving factor in several fatal cancers. Despite the great progress of RAS subtype-specific inhibitors, rapid acquired drug resistance could limit their further clinical applications. Proteolysis targeting chimera (PROTAC) has emerged as a powerful tool to handle undruggable targets and exhibited significant therapeutic benefit for the combat of drug resistance. Owing to unique molecular mechanism and binding kinetics, PROTAC is expected to become a feasible strategy to break the bottleneck of classical RAS inhibitors. This review aims to discuss the current advances of RAS inhibitors and especially focus on PROTAC strategy targeting RAS mutations and their downstream effectors for relevant cancer treatment.

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