Journal
ISCIENCE
Volume 15, Issue -, Pages 360-390Publisher
CELL PRESS
DOI: 10.1016/j.isci.2019.04.034
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Funding
- Israel Science Foundation (ISF)
- University Grants Commission (UGC), India [2277/15]
- United States-Israel Binational Science Foundation (BSF)
- Israel Cancer Research Fund (ICRF)
- National Institutes of Health [CA211752]
- EU 7th Framework Program for research, technological development, and demonstration activities [621364]
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Heparanase is an endoglycosidase involved in remodeling the extracellular matrix and thereby in regulating multiple cellular processes and biological activities. It cleaves heparan sulfate (HS) side chains of HS proteoglycans into smaller fragments and hence regulates tissue morphogenesis, differentiation, and homeostasis. Heparanase is overexpressed in various carcinomas, sarcomas, and hematological malignancies, and its upregulation correlates with increased tumor size, tumor angiogenesis, enhancedmetastasis, and poor prognosis. In contrast, knockdown or inhibition of heparanase markedly attenuates tumor progression, further underscoring the potential of anti-heparanase therapy. Heparanase inhibitors were employed to interfere with tumor progression in preclinical studies, and selected heparin mimetics are being examined in clinical trials. However, despite tremendous efforts, the discovery of heparanase inhibitors with high clinical benefit and minimal adverse effects remains a therapeutic challenge. This review discusses the key roles of heparanase in cancer progression focusing on the status of natural, chemically modified, and synthetic heparanase inhibitors in various types of malignancies.
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