Dual inhibition of GTP-bound (ON) and GDP-bound (OFF) KRASG12C suppresses PI3Kα and leads to potent tumor inhibition
Katherine Parker, Samar Ghorbanpoor, Wafa Malik, Lauren Highfield, Jamie Wang, Emily Hensley, Grace Kelley, Sarah Clark, Michela Ranieri, Soumyadip Sahu, Cathy Zhang, Magdalena A. Ploszaj, Daniel Andrussier, Hsin‐Yi Huang, Ting Chen, , Aaron N. Hata
This study shows that a dual inhibitor of KRASG12C in both ON and OFF states more effectively suppresses tumor growth than an OFF-specific inhibitor by reducing PI3K-AKT activation.
bioRxiv · Apr 30, 2026 · PreprintCancer Biology