Accumulated sotorasib-bound KRASG12C reactivates the MAPK pathway and drives sotorasib resistance via the DHX9-RAC1-PAK1 axis
Puntos clave
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.
Resumen
-mutant and sotorasib-resistant models. These findings provide previously uncharacterized mechanistic insights to guide therapeutic strategies aimed at overcoming sotorasib resistance.