Neuroendocrine phenotype as an acquired resistance mechanism in ALK-rearranged lung adenocarcinoma

Lung Cancer. 2016 Feb:92:15-8. doi: 10.1016/j.lungcan.2015.12.001. Epub 2015 Dec 4.

Abstract

A 63-year-old caucasian woman, presenting with metastatic primitive lung adenocarcinoma was treated with ALK inhibitor crizotinib treatment for six month. After rapid regression of all known lesions, tumor progression appeared six month later on all the already known lesions. A biopsy of subclavicular lymphadenopathy revealed a carcinoma with neuroendocrine phenotype with both immunohistochemical expression of ALK protein and ALK-rearrangement. It was associated with acquired resistance to crizotinib with ALK-rearrangement but without point mutation or amplification of the ALK gene. We herein report the first case of histological neuroendocrine transformation after ALK inhibitor crizotinib treatment, associated with acquired resistance to crizotinib.

Keywords: ALK; Adenocarcinoma; Crizotinib; Neuroendocrine; Non-small cell lung carcinoma.

Publication types

  • Case Reports

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / enzymology*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Adenocarcinoma of Lung
  • Anaplastic Lymphoma Kinase
  • Clavicle / pathology
  • Crizotinib
  • Drug Resistance, Neoplasm
  • Female
  • Gene Rearrangement
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / enzymology*
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Middle Aged
  • Neuroendocrine Tumors / pathology*
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazoles / therapeutic use
  • Pyridines / therapeutic use
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor Protein-Tyrosine Kinases / metabolism

Substances

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