Vascular Endothelial Growth Factor Antagonists as Anticancer Agents
Authors: Hasan, Jurjees; Jayson, Gordon C.
Source: American Journal of Cancer, Volume 3, Number 4, 2004 , pp. 229-245(17)
Publisher: Adis International
Abstract:The most potent angiogenic cytokine is vascular endothelial growth factor (VEGF). A number of strategies have been developed to inhibit the activity of the VEGF molecule and its receptors. These strategies include gene therapy techniques that deliver antisense oligonucleotides, soluble VEGF receptors that function in a dominant negative fashion, and ribozymes. Recombinant monoclonal anti-VEGF antibodies such as bevacizumab and tyrosine kinase (TK) receptor inhibitors directed against the VEGF receptors appear to be the most promising. These agents have demonstrated broad-spectrum antitumor activity in early clinical trials in a wide range of human solid tumors and hematological malignancies.
The TK receptor inhibitors are of particular interest as they can be administered orally. Early trials have reported vascular toxicities, including hemorrhagic and thromboembolic events. However, myelotoxicity is rarely seen, which enables these agents to be administered in combination with cytotoxic agents. Studies of chemotherapy and VEGF inhibitors are underway but the benefits of these regimens will need to be established in adequately powered phase III studies. Theoretically, these agents are likely to be most effective in diseases with a low tumor burden, for example, when administered as adjuvant therapy in early cancer and as maintenance therapy in advanced cancers. Other potential indications include the treatment of premalignant conditions. However, the overall development of these agents can only be optimized if appropriate biologic endpoints are identified and incorporated into clinical trials.
Document Type: Leading Article
Affiliations: Department of Medical Oncology, Cancer Research UK, Christie Hospital, Manchester, UK
Publication date: January 1, 2004