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Peer-reviewedCC BY 4.0Biochemical Journal

Uncovering KRAS-mutant allele-specific biology and vulnerabilities in non-small cell lung cancer

  • Paolo D. d'Arienzo1,2,3
  • William J. McDaid1,3
  • Kirsten L. Tinsley1,3
  • Tong Chen1,3
  • Emma J. Gasson1,3
  • Colin R. Lindsay1,2,3
  • Angeliki Malliri1,3
  1. 1Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Wilmslow Road, The University of Manchester, Manchester, U.K.
  2. 2The Christie NHS Foundation Trust, Manchester, U.K.
  3. 3Cancer Research UK Lung Centre of Excellence, Manchester, U.K.
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Abstract

KRAS (Kirsten-Ras) mutations are the most commonly occurring oncogenic drivers in non-small cell lung cancer. Despite the discovery of KRAS inhibitors representing a translational breakthrough for KRAS-driven cancers, resistance remains a major clinical challenge. We believe that to circumvent resistance, an in-depth understanding of the biological differences and therapeutic vulnerabilities specific to KRAS mutations is critical to inform rational combination partners with either mutant-selective or broad-spectrum (K)RAS inhibitors. The present review draws upon insights from both preclinical and clinical studies exploring KRAS-mutant allele-specific behaviours and therapeutic vulnerabilities. We will also highlight studies in which targeting of these vulnerabilities was combined with (K)RAS inhibitors, offering contextual examples of KRAS-mutant allele-tailored therapeutic strategies.

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Cite

BibTeXRIS
BibTeX
@article{darienzo2026uncovering,
  title = {{Uncovering KRAS-mutant allele-specific biology and vulnerabilities in non-small cell lung cancer}},
  author = {Paolo D. d'Arienzo and William J. McDaid and Kirsten L. Tinsley and Tong Chen and Emma J. Gasson and Colin R. Lindsay and Angeliki Malliri},
  journal = {Biochemical Journal},
  year = {2026},
  month = oct,
  doi = {10.1042/bcj20250138},
  url = {https://doi.org/10.1042/bcj20250138},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Uncovering KRAS-mutant allele-specific biology and vulnerabilities in non-small cell lung cancer
AU  - Paolo D. d'Arienzo
AU  - William J. McDaid
AU  - Kirsten L. Tinsley
AU  - Tong Chen
AU  - Emma J. Gasson
AU  - Colin R. Lindsay
AU  - Angeliki Malliri
PY  - 2026
DA  - 2026/10/27
JO  - Biochemical Journal
DO  - 10.1042/bcj20250138
UR  - https://doi.org/10.1042/bcj20250138
AB  - KRAS (Kirsten-Ras) mutations are the most commonly occurring oncogenic drivers in non-small cell lung cancer. Despite the discovery of KRAS inhibitors representing a translational breakthrough for KRAS-driven cancers, resistance remains a major clinical challenge. We believe that to circumvent resistance, an in-depth understanding of the biological differences and therapeutic vulnerabilities specific to KRAS mutations is critical to inform rational combination partners with either mutant-selective or broad-spectrum (K)RAS inhibitors. The present review draws upon insights from both preclinical and clinical studies exploring KRAS-mutant allele-specific behaviours and therapeutic vulnerabilities. We will also highlight studies in which targeting of these vulnerabilities was combined with (K)RAS inhibitors, offering contextual examples of KRAS-mutant allele-tailored therapeutic strategies.
SN  - 0264-6021
SN  - 1470-8728
ER  -