Abstract
Heparanase is an endo-beta-D-glucuronidase that degrades heparan sulfate glycosaminoglycan side chains of the proteoglycans in extracellular matrix and basement membrane. Heparanase enzymatic activity is important in the promotion of tumor angiogenesis, primary tumor growth, invasion, and metastasis. Expression of heparanase in many tumor types conversely correlates with prognosis. Much progress has been made in studying the regulation of heparanase expression, processing and activation. The interaction between heparanase and its substrate heparan sulfate has been well characterized. The fact that heparanase was identified as the single predominant heparan sulfate-degrading enzyme in human cancer sparked considerable interest in developing heparanase inhibitors for potential therapeutic applications. Recent progress in drug development led to several classes of heparanase inhibitors, including chemically modified natural products, small molecule inhibitors, and antibodies. Some of these inhibitors have demonstrated potent activities to inhibit tumor angiogenesis, tumor progress, or tumor metastasis. A leading compound, PI-88, is currently being evaluated in clinical phase II trials in patients with melanoma, liver, or lung cancers. This review summarizes the recent progress in heparanase biochemical research and the development of heparanase antagonists as novel anti-cancer therapeutics.
Keywords: tumor growth, metastasis, heparanase, heparan sulfate, extracellular matrix, drug development, Angiogenesis
Current Medicinal Chemistry
Title: Development of Heparanase Inhibitors for Anti-Cancer Therapy
Volume: 13 Issue: 18
Author(s): Zhenping Zhu, Elizabeth Navarro, Paul Kussie, Hu Liu and Hua-Quan Miao
Affiliation:
Keywords: tumor growth, metastasis, heparanase, heparan sulfate, extracellular matrix, drug development, Angiogenesis
Abstract: Heparanase is an endo-beta-D-glucuronidase that degrades heparan sulfate glycosaminoglycan side chains of the proteoglycans in extracellular matrix and basement membrane. Heparanase enzymatic activity is important in the promotion of tumor angiogenesis, primary tumor growth, invasion, and metastasis. Expression of heparanase in many tumor types conversely correlates with prognosis. Much progress has been made in studying the regulation of heparanase expression, processing and activation. The interaction between heparanase and its substrate heparan sulfate has been well characterized. The fact that heparanase was identified as the single predominant heparan sulfate-degrading enzyme in human cancer sparked considerable interest in developing heparanase inhibitors for potential therapeutic applications. Recent progress in drug development led to several classes of heparanase inhibitors, including chemically modified natural products, small molecule inhibitors, and antibodies. Some of these inhibitors have demonstrated potent activities to inhibit tumor angiogenesis, tumor progress, or tumor metastasis. A leading compound, PI-88, is currently being evaluated in clinical phase II trials in patients with melanoma, liver, or lung cancers. This review summarizes the recent progress in heparanase biochemical research and the development of heparanase antagonists as novel anti-cancer therapeutics.
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Cite this article as:
Zhu Zhenping, Navarro Elizabeth, Kussie Paul, Liu Hu and Miao Hua-Quan, Development of Heparanase Inhibitors for Anti-Cancer Therapy, Current Medicinal Chemistry 2006; 13 (18) . https://dx.doi.org/10.2174/092986706777935230
DOI https://dx.doi.org/10.2174/092986706777935230 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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