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. 2023 Oct 10;14:6332. doi: 10.1038/s41467-023-41828-z

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© The Author(s) 2023

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 8 — A Kaplan–Meier plot showing overall survival of lung cancer patients from TCGA database as a function of the expression of genes from the Trametinib-resistant upregulated signature (us) and KRAS mutational status. B Heatmap of biological pathways enriched by the dysregulated proteins obtained from Tram-treated parental and Tram-resistant (TR) H1792 cells 48 h after exposure to Trametinib (Tram) using METASCAPE⁷⁰. C MYC, p-MYC S62 and p-MYC T58 proteins’ expression of Parental (Par) and TR H1792 and H2009 cell lines 48 h after exposure to indicated treatments. Ctrl: Control; Tram: Trametinib (loading control: HSP90). Numbers correspond to relative MYC densitometry quantification. D Relative MYC mRNA expression of Parental (Par) and Trametinib-resistant (TR) H1792 and H2009 cell lines 24 h after Trametinib treatment. Housekeeping gene for qPCR: GAPDH (n: 3 independent experiments; data: mean +/− SD; test: two-way ANOVA, Sidak’s adjustment). E MYC protein expression in LacZ or MYC overexpressed H2009 and H358 cell lines (loading control: HSP90). F, G. Percent cell viability of LacZ or MYC overexpressed H2009 and H358 cells after 10-day treatment with increasing concentrations of Trametinib. The IC50 values for Trametinib are shown for each cell line. P values were obtained from the comparison of IC50 values between control (LacZ) and MYC-overexpressing cells (n = 4 experiments; data: mean +/− SD; test: Mann–Whitney -H2009- and t-test -H358-). H Percent cell viability of LacZ- or MYC-overexpressing H358 cells after 10-day treatment with increasing concentrations of Sotorasib. IC50 values for Sotorasib are shown for each cell line. P values were obtained from the comparison of IC50 values between control (LacZ) and MYC-overexpressing cells (n = 4 experiments; test: t-test). I Percent fold change growth of cell-derived tumors (n = 12) from LacZ- and MYC-overexpressing H358 cells treated with Sotorasib (Soto: 10 mg/Kg). (data: mean +/− SEM; test: t-test).