| AJTR Copyright © 2009-present, All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711 |
Am J Transl Res 2013;5(4):393-403
Review Article
Beyond anti-VEGF: dual-targeting antiangiogenic and antiproliferative
therapy
Chun-Te Chen, Mien-Chie Hung
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston,
TX, USA; Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University,
Taichung, Taiwan; Department of Biotechnology, Asia Univer-sity, Taichung, Taiwan
Received May 7, 2013; Accepted May 22, 2013; Epub May 24, 2013; Published June 1, 2013
Abstract: Antiangiogenesis is a promising antitumor strategy that inhibits tumor vascular formation to suppress
tumor growth. Specifically, targeting VEGF has shown therapeutic benefits in many cancer types, leading to its
approval as the first antiangiogenic drug by the Food and Drug Administration in the United States. It is known,
however, that patients will experience unfavorable side effects as the VEGF and/or VEGF receptor signaling
pathway is also required for homeostasis in normal tissues. Moreover, due to the cytostatic nature of
antiangiogenic, cancer cells that are not killed by these drugs later develop an even more malignant phenotype,
resulting in tumor invasion and metastasis. Although there have been many attempts to reduce drug resistance
and increase therapeutic efficacy by combining antiangiogenic drugs with chemotherapy, the cumulative toxicity of
antiangiogenic combinations limits their feasibility as treatments, as chronic angiogenesis inhibition typically
reduces the antitumor effect of the co-administered chemotherapeutics. To overcome these problems, it is critical
to explore new strategies that limit tumor resistance and side effects and also increase the exposure of
chemotherapy drugs at the tumor site. Here, we review current understanding of antiangiogenic drugs and
introduce a new combination strategy that links direct antiangiogenic protein and enzyme prodrug system with
dual-targeting antiangiogenic and antiproliferative therapeutic effect in tumor microenvironment. This strategy has
the potential to overcome these clinical hindrances and may serve as a paradigm for the next generation of
antiangiogenic drugs. (AJTR1305006).
Keywords: Antiangiogenesis, bevacizumab, chemotherapy, 5-fluorouracil, endothelial cell-targeting
Address correspondence to: Mien-Chie Hung, Department of Molecular and Cellular Oncology, Unit 0079, The
University of Texas MD Ander-son Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone:
713-792-3668; Fax: 713-794-0209; E-mail: mhung@mdanderson.org
Review Article
Beyond anti-VEGF: dual-targeting antiangiogenic and antiproliferative
therapy
Chun-Te Chen, Mien-Chie Hung
Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston,
TX, USA; Graduate Institute of Cancer Biology and Center for Molecular Medicine, China Medical University,
Taichung, Taiwan; Department of Biotechnology, Asia Univer-sity, Taichung, Taiwan
Received May 7, 2013; Accepted May 22, 2013; Epub May 24, 2013; Published June 1, 2013
Abstract: Antiangiogenesis is a promising antitumor strategy that inhibits tumor vascular formation to suppress
tumor growth. Specifically, targeting VEGF has shown therapeutic benefits in many cancer types, leading to its
approval as the first antiangiogenic drug by the Food and Drug Administration in the United States. It is known,
however, that patients will experience unfavorable side effects as the VEGF and/or VEGF receptor signaling
pathway is also required for homeostasis in normal tissues. Moreover, due to the cytostatic nature of
antiangiogenic, cancer cells that are not killed by these drugs later develop an even more malignant phenotype,
resulting in tumor invasion and metastasis. Although there have been many attempts to reduce drug resistance
and increase therapeutic efficacy by combining antiangiogenic drugs with chemotherapy, the cumulative toxicity of
antiangiogenic combinations limits their feasibility as treatments, as chronic angiogenesis inhibition typically
reduces the antitumor effect of the co-administered chemotherapeutics. To overcome these problems, it is critical
to explore new strategies that limit tumor resistance and side effects and also increase the exposure of
chemotherapy drugs at the tumor site. Here, we review current understanding of antiangiogenic drugs and
introduce a new combination strategy that links direct antiangiogenic protein and enzyme prodrug system with
dual-targeting antiangiogenic and antiproliferative therapeutic effect in tumor microenvironment. This strategy has
the potential to overcome these clinical hindrances and may serve as a paradigm for the next generation of
antiangiogenic drugs. (AJTR1305006).
Keywords: Antiangiogenesis, bevacizumab, chemotherapy, 5-fluorouracil, endothelial cell-targeting
Address correspondence to: Mien-Chie Hung, Department of Molecular and Cellular Oncology, Unit 0079, The
University of Texas MD Ander-son Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone:
713-792-3668; Fax: 713-794-0209; E-mail: mhung@mdanderson.org
 | |  | |  | |  | |  | |  | |  |