title: The potential of heparanase as a therapeutic target in cancer.
abstract: Heparanase has generated substantial interest as therapeutic target for antitumor therapy, because its activity is implicated in malignant behavior of cancer cells and in tumor progression. Increased heparanase expression was found in numerous tumor types and correlates with poor prognosis. Heparanase, an endoglucuronidase responsible for heparan sulfate cleavage, regulates the structure and function of heparan sulfate proteoglycans, leading to disassembly of the extracellular matrix. The action of heparanase is involved in multiple regulatory events related, among other effects, to augmented bioavailability of growth factors and cytokines. Inhibitors of heparanase suppress tumor growth, angiogenesis and metastasis by modulating growth factor-mediated signaling, ECM barrier function and cell interactions in the tumor microenvironment. Therefore, targeting heparanase has potential implications for anti-tumor, anti-angiogenic and anti-inflammatory therapies. Current approaches for heparanase inhibition include development of chemically modified heparins, small molecule inhibitors and neutralizing antibodies. The available evidence supports the emerging utility of heparanase inhibition as a promising antitumor strategy, specifically in rational combination with other agents. The recent studies with compounds designed to block heparanase (e.g., modified heparins) provide a rational basis for their therapeutic application and optimization.
authors.affiliation: Biogem, Research Institute, Ariano Irpino (AV), Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Pisano
authors.affiliation: Cancer and Vascular Biology Research Center Rappaport, Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Israel
authors.initials: I
authors.lastname: Vlodavsky
authors.affiliation: Cancer and Vascular Biology Research Center Rappaport, Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Neta
authors.initials: N
authors.lastname: Ilan
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: franco.zunino@istitutotumori.mi.it.
authors.forename: Franco
authors.initials: F
authors.lastname: Zunino
mesh_terms: D018450:Disease Progression; D005966:Glucuronidase / Q000037:antagonists & inhibitors / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology; D059016:Tumor Microenvironment; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D000099175:Heparanase
keywords: Antitumor therapy; Drug target; Heparanase; Heparanase inhibitors