August 5, 2025Open Access

Genetic mechanisms of resistance to targeted KRAS inhibition

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High-throughput screens mapped resistance mutations in non-small cell lung cancer, suggesting targeting NFκB may overcome resistance.

KRAS mutations are major drivers in non-small cell lung cancer, complicating treatment with KRAS inhibitors.
High-throughput CRISPR screens revealed specific resistance mutations to distinct KRAS-targeted therapies.
A recurrent missense mutation in capicua was linked to resistance against RMC-7977 in both lab and live models.
Targeting NFκB signaling in cells with CIC mutations showed promise in resensitizing them to RAS pathway drugs.

Diaz et al. (2025) studied this question.

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