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

Yuhui Huang; David P Carbone

doi:10.1016/j.bbcan.2015.01.003

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.

Authors

Yuhui Huang¹, David P Carbone²

Affiliations

¹ Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, Collaborative Innovation Center of Hematology, Soochow University, Suzhou, China; Department of Cancer Biology, Mayo Clinic Florida, Griffin Building Room 321B, 4500 San Pablo Road, Jacksonville, FL 32224, USA. Electronic address: hyhui20126@163.com.
² The Ohio State University Medical Center, Columbus, OH, USA. Electronic address: David.Carbone@osumc.edu.

PMID: 25598052
DOI: 10.1016/j.bbcan.2015.01.003

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