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  3. A Comprehensive Review of Marketed KRAS Inhibitors and Degraders: Challenges and Opportunities

A Comprehensive Review of Marketed KRAS Inhibitors and Degraders: Challenges and Opportunities

  • Med Res Rev. 2026 Feb 9. doi: 10.1002/med.70035.
Yi-Xin Xu 1,  Yi-Ru Bai 2,  Ruifang Li 3,  Yi-Ming Peng 1,  Ting-Ting Liu 1,  Xin Yang 1,  Ke-Tong Chen 1,  Zhi-Peng Jin 1,  Hong-Min Liu 4,  Shuo Yuan 1 2 4
Affiliations

Affiliations

  • 1 Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
  • 2 School of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou, China.
  • 3 College of Biological Engineering, Henan University of Technology, Zhengzhou, China.
  • 4 School of Pharmaceutical Sciences & Key Laboratory of Advanced Drug Preparation Technologies, Zhengzhou University, Zhengzhou, China.
PMID: 41657275 DOI: 10.1002/med.70035
Abstract

The rat sarcoma virus oncogene (Ras) is one of the most frequently mutated drivers in human cancers. Developing targeted therapies against Ras has been challenging due to its structure. The recent breakthroughs with covalent Kirsten Ras (KRAS) inhibitors represent a key milestone in targeting mutant KRAS proteins. However, drug resistance remains a significant obstacle. The proteolysis-targeting chimeras (PROTACs), which degrade mutant KRAS proteins, offer a promising strategy to overcome resistance and expand therapeutic options. This review covers the structural basis of KRAS and signaling networks, while discussing recent advancements in KRAS inhibitor research and PROTAC technology. It aims to provide a foundation and inspiration for future KRAS inhibitor and degrader development.

Keywords

KRAS; PROTAC; cancer therapy; drug resistance; inhibitor.

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