Mechanisms of and strategies for overcoming resistance to anti-vascular endothelial growth factor therapy in non-small cell lung cancer

Biochim Biophys Acta. 2015 Apr;1855(2):193-201. doi: 10.1016/j.bbcan.2015.01.003. Epub 2015 Jan 15.

Abstract

Sustained angiogenesis is a hallmark of cancer. Because of the primary role of vascular endothelial growth factors (VEGFs) and their receptors in angiogenesis, VEGF-targeted agents have been developed to inhibit these signaling processes in non-small cell lung cancer (NSCLC). However, the clinical benefits are transient and resistance often rapidly develops. Insights into the molecular mechanisms of resistance would help to develop novel strategies to improve the efficacy of antiangiogenic therapies. This review discusses the mechanisms of resistance to anti-VEGF therapy and the postulated strategies to optimize antiangiogenic therapy. A number of multitargeted tyrosine kinase inhibitors currently in phase III clinical development for NSCLC are summarized. The emerging combination of antiangiogenic therapy with tumor immunotherapy is also discussed.

Keywords: Angiogenesis; Multitargeted kinase inhibitor; NSCLC; Vascular endothelial growth factor.

Publication types

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

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Bevacizumab
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • Immunotherapy
  • Molecular Targeted Therapy*
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / genetics
  • Neovascularization, Pathologic / pathology
  • Protein Kinase Inhibitors / therapeutic use
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / genetics*

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Protein Kinase Inhibitors
  • Vascular Endothelial Growth Factor A
  • Bevacizumab