Progress of PROTAC in colorectal cancer tumor microenvironment therapy

doi:10.3877/cma.j.issn.2095-3224.2026.02.009

Abstract

Abstract:

The treatment of colorectal cancer is frequently constrained by tumour microenvironment (TME)-mediated immune suppression and multidrug resistance. Protein degradation-targeting chimeras (PROTACs) demonstrate significant potential in targeting “undruggable” molecules by recruiting E3 ubiquitin ligases to degrade target proteins. This paper provides a systematic review of PROTAC research progress in colorectal cancer therapy, with a particular emphasis on its interaction mechanisms with the TME. It explores in depth how PROTACs inhibit tumour proliferation and overcome resistance by degrading oncogenic proteins, and how they can be combined with novel delivery systems to remodel the immunosuppressive microenvironment and enhance anti-tumour immune responses. Results indicate that PROTAC technology, leveraging its precision degradation and microenvironment remodelling advantages, offers novel avenues for overcoming current therapeutic challenges in colorectal cancer.

Key words: Colorectal cancer, Proteolysis targeting chimera(PROTAC), Tumor microenvironment, Delivery system

Yichen Zhang, Yuzhou Feng, Chuanqing Bao. Progress of PROTAC in colorectal cancer tumor microenvironment therapy[J]. Chinese Journal of Colorectal Diseases(Electronic Edition), 2026, 15(02): 175-180.

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References 60

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