RAS-ON inhibition overcomes clinical resistance to KRAS G12C-OFF covalent blockade

Key Points

RAS-ON inhibition effectively overcomes clinical resistance arising against covalent KRAS G12C-OFF blockade across targeted cancer therapies.
Targeting the active RAS-ON state blocks oncogenic signaling pathways when selective KRAS G12C inhibitors encounter acquired resistance.
Analysis demonstrates that covalent blockade resistance is mitigated by direct RAS-ON inhibitors, highlighting potential for future therapy.

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Investigation reveals targeting active RAS-ON overcomes clinical resistance to covalent KRAS G12C-OFF blockade, highlighting new therapeutic options.

Selective KRAS

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Nokin et al. (2024) studied this question.

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