Targeting Heparanase in Cancer: Inhibition by Synthetic, Chemically Modified, and Natural Compounds

Chakrabhavi Dhananjaya Mohan, Swetha Hari, Habbanakuppe D. Preetham, Shobith Rangappa, Uri Barash, Neta Ilan, S. Chandra Nayak, Vijai K. Gupta, Basappa, Israel Vlodavsky*, Kanchugarakoppal S. Rangappa

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

75 Citations (Scopus)


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, enhanced metastasis, 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. Biological Sciences; Glycobiology; Molecular Biology; Cell Biology

Original languageEnglish
Pages (from-to)360-390
Number of pages31
Publication statusPrint publication - 31 May 2019
Externally publishedYes


  • Biological Sciences
  • Cell Biology
  • Glycobiology
  • Molecular Biology


Dive into the research topics of 'Targeting Heparanase in Cancer: Inhibition by Synthetic, Chemically Modified, and Natural Compounds'. Together they form a unique fingerprint.

Cite this