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. 2023 Feb 8;13:1094123. doi: 10.3389/fonc.2023.1094123

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Copyright © 2023 Sisler, Hinz, Le, Kleczko, Nemenoff and Heasley

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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KRAS^G12C inhibitors in combination with SHP2 inhibitors exhibit improved efficacy compared to either treatment alone in vivo. LLC 46 NRAS KO cells were orthotopically implanted into the left lung of C57BL/6 mice and allowed to establish for 7 days before initial pre-treatment μCT imaging. (A) Scheme showing the timeline of the experiment overlayed on tumor volume growth curves of diluent (n=5), RMC-4550 (n=6), MRTX-849 (n=7), and combination-treated (n=8) mouse cohorts. The data were analyzed by 2-way ANOVA with Tukey’s multiple comparisons test. (B) Waterfall plot showing percent change in tumor volume from pretreatment (day 7) to day 21 (11 days of treatment). The data were analyzed by Kruskal-Wallis test with Dunn’s multiple comparisons test. (C) Survival curves comparing all 4 groups over the course of the study with one-way ANOVA and multiple comparisons. ns indicates not significant.