The purpose of the current study was to evaluate hypoxia-inducible factor-1α (HIF-1α) as a novel response marker compared with previously explored markers following treatment with an EGFR-blocking monoclonal antibody (cetuximab) and a small-molecule EGFR tyrosine kinase inhibitor (gefitinib) in a group of cancer cell lines containing wild-type or tyrosine kinase domain-mutated EGFR. The gene discussed is EGFR; the disease is cancer.