What question did this study set out to answer?

This research aims to understand how accumulated sotorasib-bound KRASG12C leads to drug resistance.

May 9, 2026Open Access

Accumulated sotorasib-bound KRASG12C reactivates the MAPK pathway and drives sotorasib resistance via the DHX9-RAC1-PAK1 axis

Key Points

This research aims to understand how accumulated sotorasib-bound KRASG12C leads to drug resistance.
Developed sotorasib-resistant models to study resistance mechanisms.
Examined the role of the DHX9-RAC1-PAK1 axis in reactivating the MAPK pathway.
Utilized molecular analysis techniques to assess pathway activation.
Accumulated sotorasib-bound KRASG12C drives reactivation of the MAPK pathway.
The DHX9-RAC1-PAK1 axis is identified as a key mechanism of sotorasib resistance.
Insights from this study may inform future therapeutic strategies.

Abstract

-mutant and sotorasib-resistant models. These findings provide previously uncharacterized mechanistic insights to guide therapeutic strategies aimed at overcoming sotorasib resistance.

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Cite This Study

Zhu et al. (Fri,) studied this question.

synapsesocial.com/papers/69fece1db9154b0b82875d6e https://doi.org/https://doi.org/10.1016/j.celrep.2026.117338

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