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Crizotinib in the treatment of non-small-cell lung cancer

Patrick M Forde1, Charles M Rudin

  • 1The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD 21287, USA.

Expert Opinion on Pharmacotherapy
|May 19, 2012
PubMed
Abstract

Insights

Crizotinib effectively treats non-small-cell lung cancer (NSCLC) with echinoderm microtubule-associated protein-like 4 - anaplastic lymphoma kinase (EML4-ALK) gene rearrangements. This targeted therapy shows promise for other lung cancer subsets as well.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Lung cancer treatment advances with targeted therapies for specific driver mutations.
  • The echinoderm microtubule-associated protein-like 4 - anaplastic lymphoma kinase (EML4-ALK) fusion oncogene is found in about 5% of non-small-cell lung cancer (NSCLC).
  • Crizotinib, a tyrosine kinase inhibitor (TKI), targets the ALK fusion gene product and is approved for ALK-expressing NSCLC.

Purpose of the Study:

  • To provide an overview of ALK-associated NSCLC molecular pathogenesis.
  • To review crizotinib's pharmacokinetics and pharmacodynamics.
  • To outline preclinical and clinical studies supporting crizotinib's approval and discuss its role in treating ALK-expressing NSCLC.

Main Methods:

  • Review of molecular pathogenesis of ALK-associated NSCLC.
  • Pharmacokinetic and pharmacodynamic data analysis of crizotinib.
  • Summary of preclinical and clinical studies for crizotinib approval.

Main Results:

  • Crizotinib demonstrates efficacy in ALK-rearranged NSCLC.
  • Emerging data suggest potential activity in MET-amplified/mutated or ROS1-translocated lung cancers.
  • Crizotinib represents a targeted drug development strategy for lung cancer.

Conclusions:

  • Crizotinib is a targeted therapy for ALK-rearranged NSCLC.
  • The drug exemplifies a focused strategy based on inhibiting specific tumor mutations.
  • Crizotinib holds potential for treating other select NSCLC subsets.

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