Treatment and detection of ALK-rearranged NSCLC

Lung Cancer. 2013 Aug;81(2):145-54. doi: 10.1016/j.lungcan.2013.03.017. Epub 2013 Jun 12.

Abstract

The recent approval of crizotinib for the treatment of anaplastic lymphoma kinase (ALK)-rearranged advanced non-small cell lung cancer (NSCLC) in the US and other countries has provoked intense interest in ALK rearrangements as oncogenic drivers, and promises to revolutionise the way in which NSCLC is diagnosed and treated. Here, we review clinical data to date for the use of crizotinib to treat patients with advanced, ALK-positive NSCLC and consider issues surrounding the detection of ALK-positivity including the use of fluorescence in situ hybridisation and the other potential techniques available, and their suitability for ALK screening. We also discuss the emergence of resistance to crizotinib therapy and the range of other ALK inhibitors currently in development.

Keywords: ALK inhibitor; ALK rearrangement; Crizotinib; Diagnosis; NSCLC; Resistance.

Publication types

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

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Crizotinib
  • Gene Rearrangement
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Protein Kinase Inhibitors / therapeutic use
  • Pyrazoles / therapeutic use*
  • Pyridines / therapeutic use*
  • Receptor Protein-Tyrosine Kinases / genetics*

Substances

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