In the present study, we further characterized afatinib-resistant sublines that were independently established from the human lung cancer cell line HCC827 harboring an activated mutant EGFR and amplification of EGFR. Here we report that activation of SRC family kinases SFKs and focal adhesion kinase (FAK) is responsible for the survival of afatinib-resistant cells when expression of multiple EGFR family proteins and other receptors is diminished. This evidence concerns the gene PTK2 and lung carcinoma.