Targeted therapy for NSCLC: ALK inhibition

J Oncol Pharm Pract. 2012 Jun;18(2):271-4. doi: 10.1177/1078155211417477. Epub 2011 Aug 15.

Abstract

Purpose: The purpose of this review article is to describe the emerging data of ALK receptor tyrosine kinaase inhibitors in ALK mutation positive NSCLC.

Summary: ALK mutations have been identified in approximately 2.4-13% of patients with NSCLC, occurring more frequently in adenocarcinomas and never and light smokers. Crizotinib is an oral ATP-competitive selective inhibitor of the ALK and MET tyrosine kinases that inhibits tyrosine phosphorylation of activated ALK at nanomolar concentrations. A phase II study demonstrated an overall response rate of 57% (95% CI, 46 to 68), with the most common toxicity grade I fatigue and visual disturbances. Elevations in lever function tests were also reported.

Conclusion: The ALK receptor tyrosine kinase inhibitor crizotinib may be an effective therapy in ALK mutated NSCLC and is currently being compared to standard chemotherapy for advanced or metastatic NSCLC.

Publication types

  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / enzymology
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Clinical Trials, Phase II as Topic / methods
  • Crizotinib
  • Drug Delivery Systems / methods*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / enzymology
  • Protein Kinase Inhibitors / administration & dosage*
  • Pyrazoles / administration & dosage
  • Pyridines / administration & dosage
  • Randomized Controlled Trials as Topic / methods
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor Protein-Tyrosine Kinases / metabolism

Substances

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