EGFR controls transcriptional and metabolic rewiring in KRASG12D colorectal cancer

ABSTRACT: Inhibition of the Epidermal Growth Factor Receptor (EGFR) shows clinical benefit in metastatic colorectal cancer (CRC) patients, but KRAS-mutations are known to confer resistance. However, recent reports highlight EGFR as a crucial target to be co-inhibited with RAS inhibitors for effective treatment of KRAS-mutant CRC. Here, we investigated the tumor cell-intrinsic contribution of EGFR in KRASG12D tumors by establishing murine CRC organoids with key CRC mutations (KRAS, APC, TP53) and inducible EGFR deletion. Metabolomic, transcriptomic, and scRNA-analyses revealed that EGFR deletion in KRAS-mutant organoids reduced their phenotypic heterogeneity and activated a distinct cancer-stem-cell/WNT signature associated with reduced cell size and downregulation of major signaling cascades like MA

SUBMITTER: Dana Krauss 

PROVIDER: S-SCDT-10_1038-S44321-025-00240-4 | biostudies-other |

REPOSITORIES: biostudies-other