In the present study, we report on the development and on the characterization of human NSCLC and CRC cell lines with acquired resistance to two tyrosine kinase inhibitors (TKI) targeting the EGFR, erlotinib and gefitinib, and a TKI targeting EGFR, VEGFR and RET, vandetanib, and on the antitumor effects of sorafenib in these resistant cancer cell lines. The gene discussed is EGFR; the disease is cancer.