Histological transformation of ALK rearranged adenocarcinoma into small cell lung cancer: A new mechanism of resistance to ALK inhibitors

Lung Cancer. 2016 Dec:102:38-41. doi: 10.1016/j.lungcan.2016.10.012. Epub 2016 Oct 27.

Abstract

Various mechanisms of resistance to ALK inhibitors in ALK rearranged adenocarcinomas are reported including secondary gatekeeper mutations, bypass signaling or ALK amplifications as the commonest ones. We report a new mechanism of resistance with transformation of adenocarcinoma into small cell lung cancer. A 53-year-old non-smoker woman, experienced cancer progression after two lines of ALK inhibitors. A new biopsy showed a small cell lung cancer. FISH revealed persistent ALK rearrangement with an atypical pattern and complete loss of the 5' region of the ALK gene.

Keywords: ALK translocation; Lung neoplasms; Small cell cancer transformation.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / enzymology
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Anaplastic Lymphoma Kinase
  • Crizotinib
  • Drug Resistance, Neoplasm
  • Female
  • Gene Rearrangement
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Middle Aged
  • Mutation
  • Positron Emission Tomography Computed Tomography
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / pharmacology
  • Pyrazoles / therapeutic use*
  • Pyridines / pharmacology
  • Pyridines / therapeutic use*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Tomography Scanners, X-Ray Computed
  • Translocation, Genetic

Substances

  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines
  • Crizotinib
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases