Therefore, the 2-gene AP combinatorial mutation signature predicts responses to EGFR inhibitor therapy rather than individual mutations of APC or TP53 or KRAS. In addition, we noted that the in vitro cetuximab growth inhibition was also preferentially associated with CRC cell lines harboring APC and/or TP53 mutations, especially in the CMS2 cell lines, whereas all KRAS-mutated cell lines harboring APC and TP53 double-wild type were not sensitive to CTX. The gene discussed is EGFR; the disease is colorectal carcinoma.