Targeting ALK: a promising strategy for the treatment of non-small cell lung cancer, non-Hodgkin's lymphoma, and neuroblastoma

Target Oncol. 2012 Sep;7(3):199-210. doi: 10.1007/s11523-012-0227-8. Epub 2012 Sep 12.

Abstract

Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor that affects a number of biological and biochemical functions through normal ligand-dependent signaling. It has oncogenic functions in a number of tumors including non-small cell lung cancer (NSCLC), anaplastic large cell lymphoma, and neuroblastoma when altered by translocation or amplification or mutation. On August 2011, a small molecule inhibitor against ALK, crizotinib, was approved for therapy against NSCLC with ALK translocations. As we determine the molecular heterogeneity of tumors, the potential of ALK as a relevant therapeutic target in a number of malignancies has become apparent. This review will discuss some of the tumor types with oncogenic ALK alterations. The activity and unique toxicities of crizotinib are described, along with potential mechanisms of resistance and new therapies beyond crizotinib.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Clinical Trials as Topic
  • Crizotinib
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lymphoma, Non-Hodgkin / drug therapy*
  • Models, Genetic
  • Mutation
  • Neuroblastoma / drug therapy*
  • Oncogene Proteins, Fusion / metabolism*
  • Pyrazoles / therapeutic use
  • Pyridines / therapeutic use
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Receptor Protein-Tyrosine Kinases / metabolism*
  • Signal Transduction
  • Translocation, Genetic

Substances

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