Ryan B Corcoran, Khanh T Do, Jeong E Kim, James M Cleary, Aparna R Parikh, Oladapo O Yeku, Niya Xiong, Colin D Weekes, Jennifer Veneris, Leanne G Ahronian, Gianluca Mauri, Jun Tian, Bryanna L Norden, Alexa G Michel, Emily E Van Seventer, Giulia Siravegna, Kyle Camphausen, Gary Chi, Isobel J Fetter, Joan S Brugge, Helen X Chen, Naoko Takebe, Richard T Penson, Dejan Juric, Keith T Flaherty, Ryan J Sullivan, Jeffrey W Clark, Rebecca S Heist, Ursula A Matulonis, Joyce F Liu, Geoffrey I Shapiro
PURPOSE: MEK inhibitors (MEKi) lack monotherapy efficacy in most RAS-mutant cancers. BCL-xL is an anti-apoptotic protein identified by a synthetic lethal shRNA screen as a key suppressor of apoptotic response to MEKi. PATIENTS AND METHODS: We conducted a dose escalation study (NCT02079740) of the BCL-xL inhibitor navitoclax and MEKi trametinib in patients with RAS-mutant tumors with expansion cohorts for: pancreatic, gynecologic (GYN), non-small cell lung cancer (NSCLC), and other cancers harboring KRAS/NRAS mutations...
March 8, 2024: Clinical Cancer Research