A RAS-Independent Biomarker Panel to Reliably Predict Response to MEK Inhibition in Colorectal Cancer.

ABSTRACT: Background: In colorectal cancer (CRC), mutations of genes associated with the TGF-β/BMP signaling pathway, particularly affecting SMAD4, are known to correlate with decreased overall survival and it is assumed that this signaling axis plays a key role in chemoresistance. Methods: Using CRISPR technology on syngeneic patient-derived organoids (PDOs), we investigated the role of a loss-of-function of SMAD4 in sensitivity to MEK-inhibitors. CRISPR-engineered SMAD4^R361H PDOs were subjected to drug screening, RNA-Sequencing, and multiplex protein profiling (DigiWest^®). Initial observations were validated on an additional set of 62 PDOs with known mutational status. Results: We show that loss-of-function of SMAD4 renders PDO

SUBMITTER: Pfohl U 

PROVIDER: S-EPMC9265111 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature