Tyrosine kinase inhibitors with antiangiogenic properties for the treatment of non-small cell lung cancer

Expert Opin Investig Drugs. 2011 Jan;20(1):61-74. doi: 10.1517/13543784.2011.541153. Epub 2010 Dec 11.

Abstract

Importance of the field: The 5-year survival rate in NSCLC remains < 15% in spite of new chemotherapeutic regimens and targeted therapies. Tyrosine kinase inhibitors (TKIs) with antiangiogenic properties show promise as a new therapeutic approach for NSCLC in recent studies.

Areas covered in this review: This article reviews significant preclinical and clinical studies related to TKI therapy. Many drugs that target tyrosine kinases involved in tumor angiogenesis have recently been developed. Results of preclinical experiments and clinical trials for NSCLC are quite promising. However, response rates are low and the duration of therapeutic response is short. Mechanisms of resistance may reduce the efficacy of TKI therapy, and biomarkers of response are needed to select patients who are more likely to benefit from the therapy. Studies in mice have shown that antiangiogenic TKIs may increase metastasis, although no clear clinical evidence supports these results.

What the reader will gain: An understanding of the mechanisms of action, clinical trial results, biomarkers of response, adverse effects and possible mechanisms of resistance associated with novel TKI therapy in NSCLC.

Take home message: More preclinical and clinical research on the efficacy of TKIs in treating NSCLC is needed, but present results offer great hope for patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Non-Small-Cell Lung / blood supply
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Drug Delivery Systems
  • Drug Design
  • Drug Resistance, Neoplasm
  • Humans
  • Lung Neoplasms / blood supply
  • Lung Neoplasms / drug therapy*
  • Mice
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Survival Rate

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinase Inhibitors