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.
Export Options
About this article
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 |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Electromagnetic Energy as a Bridge Between Atomic and Cellular Levels in the Genetics Approach to Cancer Treatment
Current Topics in Medicinal Chemistry Metabolomics of Exhaled Breath Condensate by Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry: A Methodological Approach
Current Medicinal Chemistry Bortezomib: A New Pro-Apoptotic Agent in Cancer Treatment
Current Cancer Drug Targets Synthesis, Biological Profile, and Molecular Docking of Some New Bis- Imidazole Fused Templates and Investigation of their Cytotoxic Potential as Anti-tubercular and/or Anticancer Prototypes
Medicinal Chemistry Interferon-α Treatment in Systemic Mastocytosis
Current Drug Targets Urinary Tract Tumors, Biology and Risk for Artificial Sweeteners Use with Particular Emphasis on some South American Countries
Current Nutrition & Food Science Modulating Mitochondria-Mediated Apoptotic Cell Death through Targeting of Bcl-2 Family Proteins
Recent Patents on DNA & Gene Sequences The High Mobility Group A1 (HMGA1) Transcriptome in Cancer and Development
Current Molecular Medicine Discovery of Multi-target Anticancer Agents Based on HDAC Inhibitor MS-275 and 5-FU
Medicinal Chemistry Nanosuspensions of Poorly Water Soluble Drugs Prepared by Top-down Technologies
Current Pharmaceutical Design Smart Mesoporous Silica Nanocarriers for Antitumoral Therapy
Current Topics in Medicinal Chemistry Part I: Targeted Particles for Cancer Immunotherapy
Current Drug Delivery Smart Stimuli Sensitive Nanogels in Cancer Drug Delivery and Imaging: A Review
Current Pharmaceutical Design “Metabolic Reprogramming” in Ovarian Cancer Cells Resistant to Cisplatin
Current Cancer Drug Targets Retinoids in Clinical Use
Medicinal Chemistry Target Fishing of Calactin, Calotropin and Calotoxin Using Reverse Pharmacophore Screening and Consensus Inverse Docking Approach
Current Drug Discovery Technologies Innovative Strategies in In Vivo Apoptosis Imaging
Current Medicinal Chemistry Baseline Levels of Interleukine-6, Tumor-Necrosis Factor-Alpha and C-Reactive Protein in Treatment Naive Human Immunodeficiency Virus Infected Patients-A Study from a Tertiary-Care Hospital in Eastern India
Current Biomarkers (Discontinued) Bladder Cancer Stem Cells: Biological and Therapeutic Perspectives
Current Stem Cell Research & Therapy Subject index to volume 3
Current Cancer Drug Targets