Article
Disrupted molecular glue complex drives RAS inhibitor resistance.
Cell - 14 May 2026
Sang Ben, Ye Ling Feng, Fu Zheng, Pourfarjam Yasin, Cuevas-Navarro Antonio, Fan Shijie, Hu Feng, Washington Aaliyah, Rodriguez Diego J, Vides Alberto, Kar Sumit, Ahler Ethan, Lin Kevin K, Hegde Aparna, Smith Jacqueline A M, Wolpin Brian M, Punekar Salman R, Spira Alexander I, Garrido-Laguna Ignacio, Hong David S, Dar Arvin C, Yaeger Rona, Arbour Kathryn C, Lito Piro
Abstract excerpt
Tri-complex inhibitors (TCIs) are molecular glues that bind the active, guanosine triphosphate (GTP)-bound state of RAS and recruit cyclophilin A (CYPA) to form a synthetic complex that blocks oncogenic signaling. Although these agents have shown clinical activity in RAS mutant cancers, resistance mechanisms remain poorly defined. Here, we analyzed paired baseline and end-of-treatment samples from 40 patients...
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