The present studies were designed to ask whether, using traditional biochemical methods and using a minimum of DNA screening, we could define the signal transduction changes that occur when a tumor cell expressing a driving oncogene, in our case ERBB1 T790M L858R in the H1975 non-small cell lung cancer line, is made resistant to a clinically relevant standard of care drug that would be used to treat such a tumor in a patient, afatinib. Here, EGFR is linked to non-small cell lung carcinoma.