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Cancer therapy

Drugging mutant KRAS by disrupting binding to effectors and GTP

Nature Cancer volume 6, pages 228–230 (2025)Cite this article

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Although enhancing the GTPase activity of KRAS is an attractive approach to inhibit constitutively active, GTP-bound mutant KRAS, so far this has not been achieved. Now, a RAS inhibitor thought to act by preventing engagement of downstream effectors is shown to also reactivate cycling to the inactive GDP-bound state.

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Fig. 1: KRAS inhibitors exhibit distinct mechanisms of action.

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Authors and Affiliations

  1. Department of Pharmacology, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA

    Adrienne D. Cox & Channing J. Der

  2. Department of Radiation Oncology, University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA

    Adrienne D. Cox

Authors
  1. Adrienne D. Cox
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  2. Channing J. Der
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Correspondence to Adrienne D. Cox or Channing J. Der.

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Competing interests

A.D.C. has consulted for Eli Lilly and Mirati Therapeutics, a Bristol Myers Squibb company. C.J.D. is a consultant or advisory board member for AskY Therapeutics, Cullgen, Deciphera Pharmaceuticals, Kestrel Therapeutics, Mirati Therapeutics, Reactive Biosciences, Revolution Medicines and SHY Therapeutics, and has received research funding support from Deciphera Pharmaceuticals, Mirati Therapeutics, Reactive Biosciences, Revolution Medicines and SpringWorks Therapeutics.

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Cox, A.D., Der, C.J. Drugging mutant KRAS by disrupting binding to effectors and GTP. Nat Cancer 6, 228–230 (2025). https://doi.org/10.1038/s43018-025-00914-5

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