Role of mesenchymal-epithelial transition amplification in resistance to anti-epidermal growth factor receptor agents.
AffiliationCancer Research UK Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX
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AbstractAll patients with epidermal growth factor receptor (EGFR) mutant advanced non-small cell lung cancer (NSCLC) treated with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) such as gefitinib, erlotinib or afatinib will progress after a median of 9-12 months. So far, development of a secondary T790M mutation represents the most common (approximately 60%) mechanism of resistance to these drugs. The relative rarity of mesenchymal-epithelial transition (MET) amplification in NSCLC suggests that this event plays a limited role in primary resistance to EGFR-TKI. In contrast, MET gene amplification has been detected as a secondary event representing one of the most relevant mechanisms involved in the acquired resistance to EGFR-TKIs both in preclinical and clinical studies. The aim of this review is to discuss the role of MET amplification as a mechanism of resistance to anti-EGFR therapies and to review strategies which aim at overcoming this mechanism of resistance, including studies assessing drug combinations targeting both EGFR and MET pathways.
CitationRole of mesenchymal-epithelial transition amplification in resistance to anti-epidermal growth factor receptor agents. 2015, 3 (6):81 Ann Transl Med
JournalAnnals of Translational Medicine
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