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Antiangiogenic gene therapy

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A number of potent endogenous inhibitors targeting the tumor vasculature have recently been identified in tumor-bearing animals. Some of these angiogenesis inhibitors, including angiostatin, endostatin, and serpin antithrombin, seem to act specifically on the proliferating endothelial cells in the newly formed blood vessels. The discovery of these specific endothelial inhibitors not only increases our understanding of the functions of these molecules in the regulation of physiological and pathological angiogenesis, but also provides an important therapeutic strategy for cancer treatment. Several studies have demonstrated that antiangiogenic protein therapy with these inhibitors significantly suppresses the growth of a variety of tumors in mice. However, the dosages of these endogenous inhibitors used in animal studies seem to be too high for clinical trials. Other disadvantages of antiangiogenic protein therapy include repeated injections, prolonged treatment, potential transmission of toxins and infectious particles, and high cost for manufacturing large amounts of protein molecules. Thus, alternative approaches need to be developed in order to improve the antiangiogenic therapy with endogenous inhibitors. Perhaps gene therapy aimed to express these potent angiogenesis inhibitors in vivo is the most promising alternative approach that could transfer antiangiogenic therapy from animal experiments into the clinic. Although the development of this field is still in its early stages, several studies in animals have already provided evidence that this is a promising approach in the treatment of cancer. In this review article, I will discuss the therapeutic potentials of antiangiogenic molecules expressed from gene therapy vectors.

Affiliations: 1: Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden


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