Advances in Anti-Angiogenic Therapies for Cancer

Recent research from Japan, the United States, and Italy has made significant progress in the development of anti-angiogenic therapies for cancer. These studies have highlighted the potential of targeting vascular endothelial growth factor (VEGF) receptors to inhibit tumor growth and metastasis. In Japan, researchers at Taisho Pharmaceutical Co. Ltd. have identified a synthetic VEGF receptor binding antagonist, VGA1155, which exhibits anti-tumor effects in vivo by inhibiting VEGF binding to its receptors. In the United States, a study at the University of Kentucky Medical Center found that doxazosin, an alpha1-adrenoceptor antagonist, can target prostate cancer angiogenesis by inducing apoptosis in maspin-overexpressing cells.

**Key Takeaways:**

• Synthetic VEGF receptor binding antagonist, VGA1155, inhibited VEGF binding to its receptors, leading to anti-tumor effects in vivo.
• Doxazosin, an alpha1-adrenoceptor antagonist, induced apoptosis in maspin-overexpressing prostate cancer cells, suggesting its potential in anti-angiogenic therapy.
• Researchers at Sigma Tau Research Department developed a low-molecular-weight (LMW) compound, ST2184, which exhibited negligible anticoagulant activity while effectively binding VEGF and preventing its interaction with endothelial cells.
• These findings support the development of anti-angiogenic targeting therapies for various types of cancer, including prostate cancer.
• Maspin overexpression in prostate cancer cells enhanced their sensitivity to doxazosin, leading to increased apoptosis and reduced attachment to extracellular matrix-coated plates.
• The ability of maspin to sensitize prostate cancer cells to doxazosin-induced apoptosis may have therapeutic implications in the development of anti-angiogenic therapies for advanced prostate cancer.

**Statistics:**

• Jeong et al. found that synthetic VEGF receptor binding antagonist (VGA1155) exhibited anti-tumor effects in vivo, suppressing the growth of human lung, breast, colon, and epidermoid cancers in nude mouse xenograft models. (p 2005)
• Tahmatzopoulos and colleagues reported that doxazosin treatment resulted in dramatic downregulation of the 189 isoform of VEGF in maspin transfectants, while inducing a fivefold induction of Smad4 mRNA expression after 24h of treatment. (p 2005)
• Pisano and coauthors found that ST2184, a low-molecular-weight (LMW) compound, binds VEGF and prevents its interaction with endothelial cells, making it a potential anti-angiogenic agent. (p 2005)

**Sources:**

• Ueda et al. (2005). Antitumor effects of synthetic VEGF-receptor binding antagonist, VGA1155. Anticancer Res, 25(6B), 3973-3977.
• Tahmatzopoulos et al. (2005). Maspin sensitizes prostate cancer cells to doxazosin-induced apoptosis. Oncogene, 24(34), 5375-5383.
• Pisano et al. (2005). Undersulfated, low-molecular-weight glycol-split heparin as an antiangiogenic VEGF antagonist. Glycobiology, 15(2), 1C-6C.