Responses to crizotinib can occur in c-MET overexpressing nonsmall cell lung cancer after developing EGFR-TKI resistance

Cancer Biol Ther. 2019;20(2):145-149. doi: 10.1080/15384047.2018.1523851. Epub 2018 Nov 13.

Abstract

Evidence suggests that activation of the MET signaling pathway might be associated with EGFR-TKI resistance. EGFR TKI-resistant lung cancers often remain sensitive to inhibition of the EGFR pathway; thus, c-MET inhibitors are likely to be effective when combined with continued EGFR-TKI treatment. Here, we described a 56-year-old male who became refractory after first-line gefitinib therapy and was confirmed to have c-MET overexpression without a T790M mutation, c-MET amplification or MET exon 14 alterations. A complete response to crizotinib occurred in this patient. Our case report uncovered the underlying mechanism of c-MET overexpression in affecting EGFR-TKI sensitivity, and crizotinib may assist in overcoming this problem.

Keywords: EGFR; EGFR-TKI; NSCLC; c-MET; crizotinib; gefitinib; resistance.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Crizotinib / pharmacology
  • Crizotinib / therapeutic use*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins c-met / genetics*

Substances

  • Protein Kinase Inhibitors
  • Crizotinib
  • Proto-Oncogene Proteins c-met

Grants and funding

This work was supported by Natural Scientific Foundation of Zhejiang Province (LGF18H160017). The funders had no role in data collection, decision to publish, or preparation of the manuscript.