Extended Data Fig. 10: MRTX1133 treatment regulates key KRAS-dependent oncogenic signaling and feedback inhibitory pathways in vivo.
From: Anti-tumor efficacy of a potent and selective non-covalent KRASG12D inhibitor
(a) Heatmap depicting GSEA Hallmark signatures altered in the AsPC-1 xenograft model by MRTX1133 treatment, or the combination of MRTX1133 with cetuximab treatment, at 6 and 24 hours after either 3 doses (BID + 1) or BID dosing for 7 days (BID × 7) as compared to vehicle-treated AsPC-1 tumors (n = 3/time point). NES = normalized enrichment score, * = false discovery rate (FDR) < 0.25. (b) Heatmap depicting differential expression of MAPK associated gene sets in MRTX1133 treatment or MRTX1133 and cetuximab combination treatment after 6- and 24-hours treatment with either 3 doses (BID + 1) or BID dosing for 7 days (BID × 7) in AsPC-1 tumors or single dose in LS180 tumors, as compared to vehicle-treated tumors (n = 3/time point). * = -log(FDR) > 1.3 (FDR < 0.05). (c) Heatmap depicting differential expression of tumor suppressor, pro-apoptotic, pro-survival, and cell cycle associated gene sets following MRTX1133 treatment or MRTX1133 and cetuximab combination treatment after 6 and 24 hours treatment with either 3 doses (BID + 1) or BID dosing for 7 days (BID × 7) in AsPC-1 tumors or single dose in LS180 tumors, as compared to vehicle-treated tumors (n = 3/time point). ‘*’ = -log(FDR) > 1.3 (FDR < 0.05).
