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Comment
. 2023 Sep 15;29(18):3563-3565.
doi: 10.1158/1078-0432.CCR-23-1658.

Targeting KRAS-Mutated NSCLC: Novel TKIs and Beyond

David J Cantor  1 , Charu Aggarwal  1   2   3
Affiliations
Comment

Targeting KRAS-Mutated NSCLC: Novel TKIs and Beyond

David J Cantor et al. Clin Cancer Res. .

Abstract

KRAS-mutated non-small cell lung cancer (NSCLC) is the most common genetically altered subtype of NSCLC, yet targeted therapies remain limited. Multiple studies have investigated combinations of MEK inhibitors with chemotherapy without success. Here we discuss these studies and novel approaches to targeting KRAS-mutated NSCLC. See related article by Gadgeel et al., p. 3641.

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Conflict of interest statement

Disclosure of Potential Conflicts of Interest:

Dr. Cantor has no conflicts of interest to report. Dr. Aggarwal reports receiving institutional research funding from AstraZeneca, Genentech, Incyte, Macrogenics, Medimmune, and Merck Sharp & Dohme, and receiving consultation fees from Genentech, Lilly, Celgene Merck, AstraZeneca, Blueprint Genetics, Shionogi, Daiichi Sankyo/ Astra Zeneca, Regeneron/ Sanofi, Eisai, BeiGene, Turning Point, Pfizer, Janssen, Boehringer Ingelheim.

Figures

None
Strategies for targeting KRASm NSCLC. Represented is canonical KRAS signaling. In its inactive state, KRAS is bound to GDP. Following activation of membrane receptors, KRAS bound GDP is exchanged for GTP resulting in KRAS activation. KRAS subsequently activates downstream signaling pathways such as the MAP/ERK and PI3K/AKT pathway leading to cellular proliferation and survival. Mutant KRAS as well as upstream and downstream effectors of the KRAS pathway are targets for small molecule inhibitors. Strategies to activate the anti-tumor immune response includes immune checkpoint inhibitors, engineered T cells expressing KRASm TCRs, and mRNA vaccines expressing KRASm neoantigens. Created with BioRender.com
See this image and copyright information in PMC

Comment on

References

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