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Noninvasive detection of EGFR T790M in gefitinib or erlotinib resistant non-small cell lung cancer

Clinical Cancer Research, ISSN: 1078-0432, Vol: 15, Issue: 8, Page: 2630-2636
2009
  • 227
    Citations
  • 0
    Usage
  • 139
    Captures
  • 1
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    227
    • Citation Indexes
      218
    • Patent Family Citations
      5
      • Patent Families
        5
    • Clinical Citations
      2
      • PubMed Guidelines
        2
    • Policy Citations
      2
      • Policy Citation
        2
  • Captures
    139
  • Mentions
    1
    • Blog Mentions
      1
      • Blog
        1

Article Description

Purpose: Tumors from 50% of epidermal growth factor receptor (EGFR) mutant non - small cell lung cancer patients that develop resistance to gefitinib or erlotinib will contain a secondary EGFR T790M mutation. As most patients do not undergo repeated tumor biopsies we evaluated whether EGFR T790M could be detected using plasma DNA. Experimental Design: DNA from plasma of 54 patients with known clinical response to gefitinib or erlotinib was extracted and used to detect both EGFR-activating and EGFR T790M mutations. Forty-three (80%) of patients had tumor EGFR sequencing (EGFR mutant/wild type: 30/13) and seven patients also had EGFR T790M gefitinib/erlotinib-resistant tumors. EGFR mutations were detected using two methods, the Scorpion Amplification Refractory Mutation System and theWAVE/Surveyor, combined with whole genome amplification. Results: Both EGFR-activating and EGFR T790M were identified in 70% of patients with known tumor EGFR-activating (21 of 30) orT790M (5 of 7) mutations. EGFR T790M was identified from plasma DNA in 54% (15 of 28) of patients with prior clinical response to gefitinib/erlotinib, 29% (4 of 14) with prior stable disease, and in 0% (0 of 12) that had primary progressive disease or were untreated with gefitinib/erlotinib. Conclusions: EGFR T790M can be detected using plasma DNA from gefitinib- or erlotinib- resistant patients. This noninvasive method may aid in monitoring drug resistance and in directing the course of subsequent therapy. © 2009 American Association for Cancer Research.

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