EGFR T790M: Revealing the secrets of a gatekeeper

Brian Ko, Daniel Paucar, Balazs Halmos

Research output: Contribution to journalReview articlepeer-review

44 Scopus citations


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 languageEnglish (US)
Pages (from-to)147-159
Number of pages13
JournalLung Cancer: Targets and Therapy
StatePublished - Oct 9 2017


  • Epidermal growth factor receptor
  • Lung cancer
  • Resistance
  • T790M
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology


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