Tyrosine kinase inhibitor acquired resistance mechanism alternates between EGFR and ALK in a lung adenocarcinoma patient

Thorac Cancer. 2019 May;10(5):1252-1255. doi: 10.1111/1759-7714.13015. Epub 2019 Feb 20.


Drive gene mutation positive non-small cell lung cancer achieves reliable clinical responses to subsequent target therapy. However, most patients will inevitably develop disease progression with multiple treatment failure. Next generation sequencing can identify clear resistance mechanisms. We report a case of a late stage, non-smoking, male non-small cell lung cancer patient that developed dual mutations and our attempts to determine the novel resistance mechanism. After systematic chemotherapy, he was administered multiple target therapy according to different genotypes. Larger panel gene detection was adapted after the failure of different treatments to investigate the resistance mechanism. Re-biopsy and large panel NGS revealed an EGFR mutant lung adenocarcinoma with alternating changes in acquired resistance between EGFR and ALK. The total survival time was 73 months. The genotypes and treatments in this patient provide new insight of target therapy resistance mechanisms. Re-biopsy and large panel gene detection should be performed for each driver gene mutation to provide precision treatment strategies.

Keywords: ALK; Acquired resistance mechanism; alternate EGFR; lung cancer.

Publication types

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

MeSH terms

  • Adenocarcinoma of Lung / diagnosis
  • Adenocarcinoma of Lung / drug therapy*
  • Adenocarcinoma of Lung / genetics*
  • Adult
  • Alleles
  • Anaplastic Lymphoma Kinase / chemistry
  • Anaplastic Lymphoma Kinase / genetics*
  • Biomarkers, Tumor
  • Biopsy
  • Drug Resistance, Neoplasm / genetics*
  • ErbB Receptors / chemistry
  • ErbB Receptors / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • Models, Molecular
  • Mutation
  • Positron Emission Tomography Computed Tomography
  • Protein Conformation
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use*
  • Structure-Activity Relationship


  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors