Researchers have identified a specific protein, RASH3D19, that is responsible for activation of RAS signaling pathways involved in aggressive tumor growth and resistance to KRAS inhibitors in patients with KRAS-mutant cancers. Blocking RASH3D19 in combination with KRAS inhibitors improved outcomes in preclinical models, suggesting this combination as a potential therapeutic strategy for patients with KRAS-mutant cancers. The study was led by Subrata Sen, Ph.D., deputy chair of Translational Molecular Pathology, and Hiroshi Katayama, Ph.D., associate professor of Translational Molecular Pathology, along with co-first authors, Warapen Treekitkarnmongkol, Ph.D., and Deivendran Sankaran, Ph.D.
“These findings provide crucial clarity on the mechanisms of RAS pathway activation, identify an actionable target responsible for aggressive disease in patients with KRAS-mutant cancers, and provide insights into the development of resistance to KRAS-targeting drugs. This has significant clinical implications that can, hopefully, improve outcomes for patients,” Sen said.