Year: 2017
Type: article
Abstract: : Non-small-cell lung cancers that harbor activating mutations in the EGFR gene represent an important molecularly defined subset of lung cancer. Despite dramatic initial responses with first- and second-generation EGFR-directed tyrosine-kinase inhibitors (TKIs) against these cancers, the development of a dominant and frequent resistance mechanism through a threonine–methionine amino acid substitution at position 790 (T790M) of EGFR has limited the long-term efficacy of these targeted therapies. This “gatekeeper” EGFR T790M alteration remains the only validated and relevant second-site resistance mutation for EGFR , allowing for focused research to understand and overcome EGFR T790M-mediated resistance. The current review focuses on EGFR T790M by discussing mechanisms of resistance mediated by EGFR T790M, reviewing development of novel third-generation EGFR TKIs targeting EGFR T790M, and highlighting current research on overcoming resistance to third-generation EGFR T790M TKIs. Keywords: lung cancer, epidermal growth factor receptor, T790M, targeted therapy, resistance
Source: Lung Cancer Targets and Therapy
DOI: 10.2147/lctt.s117944
Authors: Brian Ko, Daniel Paucar, Balazs Halmos
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,320
OpenAlex ID: W2760944698