Crizotinib in the treatment of non-small-cell lung cancer. Review uri icon

Overview

abstract

  • INTRODUCTION: Recent progress in identifying distinct subsets of lung cancer, based on critical driver mutations, has led to increasingly focused efforts in the development of selectively targeted therapies. The fusion oncogene, echinoderm microtubule-associated protein-like 4 - anaplastic lymphoma kinase (EML4-ALK), is present in approximately 5% of non-small-cell lung cancer (NSCLC) tumors. Crizotinib is an oral tyrosine kinase inhibitor (TKI), which silences the protein product of the ALK fusion gene and has recently been approved for the treatment of NSCLC aberrantly expressing ALK. Emerging data suggest that crizotinib may also have activity in other subsets of lung cancer, including tumors demonstrating amplification or mutation of the MET oncogene, or translocation of the ROS1 oncogene. AREAS COVERED: This paper gives an overview of the molecular pathogenesis of ALK-associated NSCLC. It also reviews the pharmacokinetic and pharmacodynamic data on crizotinib and outlines the preclinical and clinical studies leading to the approval of crizotinib. In addition, it discusses its role in the treatment of NSCLC expressing ALK. EXPERT OPINION: Crizotinib represents the newest example of a focused strategy for drug development in lung cancer, based on identification and targeted inhibition of critical tumor-specific driver mutations. Crizotinib has demonstrated efficacy against ALK-rearranged NSCLC, and has potential for broader application in select subsets of lung cancer.

publication date

  • June 1, 2012

Research

keywords

  • Antineoplastic Agents
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyridines

Identity

Scopus Document Identifier

  • 84861313207

Digital Object Identifier (DOI)

  • 10.1517/14656566.2012.688029

PubMed ID

  • 22594847

Additional Document Info

volume

  • 13

issue

  • 8