KRAS mutant and RAS/BRAF wild type colorectal cancer cells exhibit differences in the rewiring of signal transduction that can impact on future therapeutic strategies


Background: KRAS mutant (KRAS MT) and RAS/BRAF wild type (RAS WT) colorectal cancer (CRC) responds differently to targeted agents. A better understanding of early effects on signal transduction following exposure to targeted agents may explain this and inform future therapeutic strategies.

Methods: A panel of 25 CRC cell lines (10 KRAS MT, 15 RAS WT) and 13 samples isolated from CRC patients’ (pt) serous effusions were used. Using a multiplex antibody-based platform, simultaneous changes in 60 phosphorylated (p) proteins were quantified following 1-hour exposure to clinically used concentrations of: gefitinib, PI3K inhibitor: pictilisib, AZD5363, everolimus, trametinib and vemurafenib. Statistical analysis included logistic regression, T tests and Spearman’s correlation.

Annals of Oncology