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.
Original language | English (US) |
---|---|
Pages (from-to) | 147-159 |
Number of pages | 13 |
Journal | Lung Cancer: Targets and Therapy |
Volume | 8 |
DOIs | |
State | Published - Oct 9 2017 |
Keywords
- Epidermal growth factor receptor
- Lung cancer
- Resistance
- T790M
- Targeted therapy
ASJC Scopus subject areas
- Oncology