Several studies have now evaluated the association between single genes or microRNAs (EREG/AREG, HER2, HER3, EPHA2, or mir-31-3p) and responses to anti-EGFR therapy.20 In contrast, we evaluated a refined form of our previously published gene expression signature (with multiple genes) to identify biologically different CRC subtypes with distinct cellular phenotypes.5,16 The subtypes summarize a complex network of pathways potentially associated with therapeutic responses, simplifying multiple levels of information derived from heterogeneous samples. This evidence concerns the gene EPHA2 and colorectal carcinoma.