Article
Phase I/II Study of Combined BCL-xL and MEK Inhibition with Navitoclax and Trametinib in KRAS or NRAS Mutant Advanced Solid Tumors.
Clinical cancer research : an official journal of the American Association for Cancer Research - 1 May 2024
Corcoran Ryan B, Do Khanh T, Kim Jeong E, Cleary James M, Parikh Aparna R, Yeku Oladapo O, Xiong Niya, Weekes Colin D, Veneris Jennifer, Ahronian Leanne G, Mauri Gianluca, Tian Jun, Norden Bryanna L, Michel Alexa G, Van Seventer Emily E, Siravegna Giulia, Camphausen Kyle, Chi Gary, Fetter Isobel J, Brugge Joan S, Chen Helen, Takebe Naoko, Penson Richard T, Juric Dejan, Flaherty Keith T, Sullivan Ryan J, Clark Jeffrey W, Heist Rebecca S, Matulonis Ursula A, Liu Joyce F, Shapiro Geoffrey I
Abstract excerpt
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:...
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