ROS1 [corrected]

J Clin Pathol. 2017 Dec;70(12):1001-1009. doi: 10.1136/jclinpath-2016-204244. Epub 2017 Sep 13.

Abstract

ROS1 is a receptor tyrosine kinase that has recently been shown to undergo gene rearrangements in~1%-2% of non-small cell lung carcinoma (NSCLC) and in a variety of other tumours including cholangiocarcinoma, gastric carcinoma, colorectal carcinoma and in spitzoid neoplasms, glioblastoma and inflammatory myofibroblastic tumours. The ROS1 gene fusion undergoes constitutive activation, regulates cellular proliferation and is implicated in carcinogenesis. ROS1 fusions can be detected by fluorescence in situ hybridisation, real-time PCR, sequencing-based techniques and immunohistochemistry-based methods in clinical laboratories. The small molecule tyrosine kinase inhibitor, crizotinib has been shown to be an effective inhibitor of ROS1 and has received Food and Drug Administration approval for treatment of advanced NSCLC. The current review is an update on the clinical findings and detection methods of ROS1 in clinical laboratories in NSCLC and other tumours.

Keywords: cancer; cancer genetics; lung cancer.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / antagonists & inhibitors
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Crizotinib
  • Gene Expression Regulation, Neoplastic
  • Gene Fusion
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / therapeutic use
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / metabolism
  • Pyrazoles / therapeutic use
  • Pyridines / therapeutic use
  • Signal Transduction

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Pyrazoles
  • Pyridines
  • Crizotinib
  • Protein-Tyrosine Kinases
  • ROS1 protein, human