Targeting the EGFR T790M mutation in non-small-cell lung cancer

Research output: Contribution to journalReview articlepeer-review


Introduction: The presence of activating mutations of the epidermal growth factor receptor (EGFR) is predictive of response to first- and second-generation tyrosine kinase inhibitors (TKIs) in patients with advanced non-small-cell lung cancer (NSCLC). However, patients that initially respond to these drugs inexorably become resistant. The T790M mutation in the exon 20 of the EGFR is the main mechanism of resistance to EGFR TKIs occurring in over 50% of the cases. Third generation EGFR TKIs have been shown to be active in patients who progressed after TKI treatment and carry the T790M mutation. Areas covered: This review is focused on the implications of tumor heterogeneity for targeting the T790M in patients with NSCLC. Expert opinion: Pre-clinical and clinical data suggest that the T790M is heterogeneously expressed in tumors that become resistant to first- and second-generation EGFR TKIs. These findings have important implications for the molecular diagnostic of the T790M mutation. Indeed, the analysis of both the circulating free tumor DNA (ctDNA) isolated from plasma and the tumor tissue might provide complimentary information to identify patients carrying the T790M mutation. However, further studies are needed to better understand the influence of tumor heterogeneity on the activity of drugs targeting the T790M.

Original languageEnglish
Pages (from-to)159-165
Number of pages7
JournalExpert Opinion on Therapeutic Targets
Issue number2
Publication statusPublished - Feb 1 2017


  • EGFR
  • resistance
  • T790M
  • tumor heterogeneity
  • tyrosine kinase inhibitors

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Clinical Biochemistry


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