EGFR and non-small cell lung carcinoma: Preclinical studies using NSCLC cell lines have also demonstrated that activation of the JAK2/STAT3 pathway can also substitute for EGFR signaling, while increased levels of insulin growth factor-1 receptor (IGFR-1) and constitutive activation of the IGFR-1 pathway was reported in gefitinib- or erlotinib-resistant lung cancer cell lines and gefitinib-resistant tumors in patients with NSCLC (139).