ALK rearrangements: Biology, detection and opportunities of therapy in non-small cell lung cancer

Crit Rev Oncol Hematol. 2019 Apr:136:48-55. doi: 10.1016/j.critrevonc.2019.02.006. Epub 2019 Feb 16.

Abstract

The ALK receptor tyrosine kinase (ALK) gene encodes a transmembrane protein rearranged in 2-7% of non-small cell lung cancer (NSCLC) cases. This gene has become the second most studied therapeutic target after EGFR due to the implied therapeutic opportunities. While the diagnostic of ALK rearrangements is well established, small molecules targeting ALK are in constant evolution because tumor cells eventually will develop mechanisms of resistance. In this review we describe the biology of the ALK gene, alterations, epidemiology, diagnostic tests as well as strategies of treatment.

Keywords: ALK; Diagnostic tests; Non-small cell lung cancer; Tyrosine-kinase inhibitors.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase / antagonists & inhibitors
  • Anaplastic Lymphoma Kinase / genetics*
  • Anaplastic Lymphoma Kinase / metabolism
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung* / diagnosis
  • Carcinoma, Non-Small-Cell Lung* / drug therapy
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • Cell Transformation, Neoplastic / genetics
  • DNA Mutational Analysis / methods*
  • Early Detection of Cancer / methods
  • Humans
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / drug therapy
  • Lung Neoplasms* / genetics
  • Molecular Targeted Therapy / methods
  • Molecular Targeted Therapy / trends
  • Mutation*
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Receptor Protein-Tyrosine Kinases