Antiangiogenic gene therapy of cancer: recent developments
- PDF / 1,542,451 Bytes
- 20 Pages / 610 x 792 pts Page_size
- 9 Downloads / 219 Views
BioMed Central
Open Access
Review
Antiangiogenic gene therapy of cancer: recent developments Anita Tandle†, Dan G Blazer III† and Steven K Libutti* Address: Surgery Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892 USA Email: Anita Tandle - [email protected]; Dan G Blazer - [email protected]; Steven K Libutti* - [email protected] * Corresponding author †Equal contributors
Published: 25 June 2004 Journal of Translational Medicine 2004, 2:22
doi:10.1186/1479-5876-2-22
Received: 17 May 2004 Accepted: 25 June 2004
This article is available from: http://www.translational-medicine.com/content/2/1/22 © 2004 Tandle et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
Abstract With the role of angiogenesis in tumor growth and progression firmly established, considerable effort has been directed to antiangiogenic therapy as a new modality to treat human cancers. Antiangiogenic agents have recently received much widespread attention but strategies for their optimal use are still being developed. Gene therapy represents an attractive alternative to recombinant protein administration for several reasons. This review evaluates the potential advantages of gene transfer for antiangiogenic cancer therapy and describes preclinical gene transfer work with endogenous angiogenesis inhibitors demonstrating the feasibility of effectively suppressing and even eradicating tumors in animal models. Additionally, we describe the advantages and disadvantages of currently available gene transfer vectors and update novel developments in this field. In conclusion, gene therapy holds great promise in advancing antiangiogenesis as an effective cancer therapy and will undoubtedly be evaluated in human clinical trials in the near future.
Introduction In 1971, Dr. Judah Folkman first proposed the hypothesis that tumor growth is angiogenesis dependent [1]. Angiogenesis, the growth of new capillary blood vessels from preexisting vasculature, has long been appreciated for its role in normal growth and development and now is widely recognized for its role in tumor progression and metastasis [2]. Angiogenesis is a multi-step process that includes endothelial cell (EC) proliferation, migration, basement membrane degradation, and new lumen organization. Within a given microenvironment, the angiogenic response is determined by a net balance between pro- and anti-angiogenic regulators released from activated ECs, monocytes, smooth muscle cells and platelets. The principal growth factors driving angiogenesis are vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and hepatocyte growth factor. Other positive regulators are angiotropin, angiogenin, epidermal growth factor, granulocyte colony-stimulating
factor, interleukin-1 (IL-1), IL-6, IL-8, platelet-derived growth factor (PDGF), tumor necrosis fact
Data Loading...
