Jason R. Williams, Founder and Director of Interventional Oncology and Immunotherapy at Williams Cancer Institute, shared a post on X:
”45% of patients on daraxonrasib developed acquired resistance, converging on the same target through different routes. KRAS Y64 mutations disrupt the molecular glue directly.
Y71 mutations and hypoactive BRAF enhance native RAS-RAF binding so the inhibitor can’t displace it. One protein, multiple escape doors. Cancer is pleiotropic. The chemistry has to be.”
Title: Disrupted molecular glue complex drives RAS inhibitor resistance
Authors: Ben Sang, Ling Feng Ye, Zheng Fu, Yasin Pourfarjam, Antonio Cuevas-Navarro, Shijie Fan, Feng Hu, Aaliyah Washington, Diego J. Rodriguez, Alberto Vides, Sumit Kar, Ethan Ahler, Kevin K. Lin, Aparna Hegde, Jacqueline A. M. Smith, Brian M. Wolpin, Salman R. Punekar, Alexander I. Spira, Ignacio Garrido-Laguna, David S. Hong, Arvin C. Dar, Rona Yaeger, Kathryn C. Arbour, Piro Lito
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