The Relative Expression of Mig6 and EGFR Is Associated with Resistance to EGFR Kinase Inhibitors

摘要: The sensitivity of only a few tumors to anti-epidermal growth factor receptor EGFR tyrosine kinase inhibitors (TKIs) can be explained by the presence (TK) domain mutations. In addition, such mutations were rarely found in tumor types other than lung, as pancreatic and head neck cancer. this study we sought elucidate mechanisms resistance EGFR-targeted therapies that do not harbor TK sensitizing order identify markers capable guiding decision incorporate these drugs into chemotherapeutic regimens. Here show activity was markedly decreased during evolution inhibitor (TKI) erlotinib, with concomitant increase mitogen-inducible gene 6 (Mig6), negative regulator through upregulation PI3K-AKT pathway. activity, which more accurately predicted ratio Mig6/EGFR, highly correlated erlotinib panels cancer cell lines different tissue origins. Blinded testing analysis prospectively followed cohort lung patients treated gefitinib alone demonstrated higher response rates marked increased progression free survival for low Mig6/EGFR (approximately 100 days, P = 0.01).