Article
Co-targeting SOS1 enhances the antitumor effects of KRASG12C inhibitors by addressing intrinsic and acquired resistance.
Nature cancer - 1 Sept 2024
Thatikonda Venu, Lyu Hengyu, Jurado Sabine, Kostyrko Kaja, Bristow Christopher A, Albrecht Christoph, Alpar Donat, Arnhof Heribert, Bergner Oliver, Bosch Karin, Feng Ningping, Gao Sisi, Gerlach Daniel, Gmachl Michael, Hinkel Melanie, Lieb Simone, Jeschko Astrid, Machado Annette A, Madensky Thomas, Marszalek Ethan D, Mahendra Mikhila, Melo-Zainzinger Gabriella, Molkentine Jessica M, Jaeger Philipp A, Peng David H, Schenk Robyn L, Sorokin Alexey, Strauss Sandra, Trapani Francesca, Kopetz Scott, Vellano Christopher P, Petronczki Mark, Kraut Norbert, Heffernan Timothy P, Marszalek Joseph R, Pearson Mark, Waizenegger Irene C, Hofmann Marco H
Abstract excerpt
Combination approaches are needed to strengthen and extend the clinical response to KRASG12C inhibitors (KRASG12Ci). Here, we assessed the antitumor responses of KRASG12C mutant lung and colorectal cancer models to combination treatment with a SOS1 inhibitor (SOS1i), BI-3406, plus the KRASG12C inhibitor, adagrasib. We found that responses to BI-3406 plus adagrasib were stronger than to adagrasib alone, comparable...
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