In vitro and in vivo studies generally include the generation of resistant cells to anti-EGFR therapy by a long-time exposure of cetuximab or panitumumab sensitive cells, followed by molecular characterization of the resistant cells compared to paired initially sensitive cells, and ideally functional studies to confirm causality of the preclinical findings, as well as confirmation of the preclinical findings in tumor samples from patients treated with anti-EGFR therapy. Here, EGFR is linked to neoplasm.