[Crizotinib for ROS1-rearranged non-small cell lung cancer patients]

Bull Cancer. 2017 Apr;104(4):303-310. doi: 10.1016/j.bulcan.2017.01.008. Epub 2017 Feb 22.
[Article in French]

Abstract

ROS1 fusions are rare mutations that preferentially concern young and non-smoker women. The ROS1-rearranged protein conserves an intact tyrosine kinase domain, leading to the constitutive activation of the ROS1 tyrosine kinase function and of its downstream pathways, that are known to be involved in tumorigenesis. These molecular abnormalities have shown their oncogenic potential in animals' models and in human, with an early effect on carcinogenesis. Several partners have been identified. Patients with non-small cell lung cancers (NSCLC) harbouring ROS1 alterations can receive specific targeted therapies. Indeed, crizotinib has recently been approved in France in advanced ROS1-rearranged NSCLC. We propose a review of the oncogenic role of ROS1 rearrangements, the different methods for its diagnosis, and the available treatments.

Keywords: Cancer bronchique non à petites cellules; Crizotinib; Non-small cell lung cancer; ROS1-positive; Réarrangement de ROS1.

MeSH terms

  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Clinical Trials as Topic
  • Crizotinib
  • Drug Approval
  • Drug Resistance, Neoplasm / genetics
  • Gene Rearrangement*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Molecular Targeted Therapy / methods
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / physiology
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins / physiology
  • Pyrazoles / therapeutic use*
  • Pyridines / therapeutic use*
  • Signal Transduction

Substances

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