TEM8 Targeted Cancer Therapy

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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  • 27th of 59 in Chemistry, Medicinal

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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TEM8 Targeted Cancer Therapy



Anti-Cancer Agents in Medicinal Chemistry, 11(10): 983-992.

Author(s): Arthur E. Frankel, Carol Carter, Shu-Ru Kuo, Jung-Hee Woo, Jeremy Mauldin and Jen-Sing Liu.

Affiliation: 5701 South Airport Rd, Scott&White Cancer Research Institute, Temple, TX 76502, USA.

Abstract

Tumor growth depends upon access to host blood vessels. Many steps in tumor angiogenesis have been defined including tumor cell hypoxia, tumor cell secretion of pro-angiogenic growth factors, receptor activation on host endothelium and stroma, and establishment of new blood vessels feeding the tumor mass. Inhibitors for some of these steps have been synthesized and tested clinically. While modest improvements in response, progression-free survival and overall survival have been observed in metastatic colorectal carcinoma, non-small cell lung carcinoma, breast carcinoma, renal cell carcinoma, and glioblastoma, almost all patients ultimately relapse and die from metastatic disease. Explanations for the limited effects of anti-angiogenesis therapy include lack of activity on all the parallel angiogenic pathways, non-specific toxicities of some of the agents, induction of a pro-metastatic phenotype by the enhanced hypoxia from therapy, and lack of effect on already established tumor blood vessels. One solution is to directly attack the tumor vasculature rather than inhibit tumor vessel formation. The flavonoid ASA404 and the tubulin-binder combretastatin A-4 phosphate directly damage tumor endothelium by different mechanisms. Both compounds have shown minimal single agent disease activity and produce cardiac ischemia in clinical trials. Recently, ligand-directed vascular disrupting agents have been synthesized and tested. A promising member of this class of therapeutics targets the tumor endothelial marker-8 (TEM8). Anti-TEM8 antibody drug conjugate may facilitate selective destruction of tumor blood vessels yielding enhanced anti-cancer efficacy and reduced normal tissue toxicities. Advances in this field are described which should lead to clinical studies of TEM8 targeted cancer therapeutics.

Keywords:

Angiogenesis, antibody drug conjugate, ligand-directed vascular disrupting agents, TEM8, vascular endothelial growth factors (VEGFs), tyrosine kinase inhibitors, monoclonal antibodies, fibronectin, vitronectin receptor.



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Article Details

Volume: 11
Issue Number: 10
First Page: 983
Last Page: 992
Page Count: 10
DOI: 10.2174/187152011797927643
Price: $58
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