Journal
CANCER LETTERS
Volume 382, Issue 2, Pages 245-254Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2016.09.004
Keywords
Heparan sulfate proteoglycan; Heparanase; Heparanase inhibitor; Heparan sulfate mimetic; Sarcoma
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Funding
- Associazione Italiana per la Ricerca sul Cancro [IG 8956]
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Heparanase, the only known mammalian endoglycosidase degrading heparan sulfate (HS) chains of HS proteoglycans (HSPG), is a highly versatile protein affecting multiple events in tumor cells and their microenvironment. In several malignancies, deregulation of the heparanase/HSPG system has been implicated in tumor progression, hence representing a valuable therapeutic target. Currently, multiple agents interfering with the heparanase/HSPG axis are under clinical investigation. Sarcomas are characterized by a high biomolecular complexity and multiple levels of interconnection with microenvironment sustaining their growth and progression. The clinical management of advanced diseases remains a challenge. In several sarcoma subtypes, high levels of heparanase expression have been correlated with poor prognosis associated factors. On the other hand, expression of cell surface-associated HSPGs (i.e. glypicans and syndecans) has been found altered in specific sarcoma subtypes. Recent studies provided the pre-clinical proof-of-principle of the role of the heparanase/HSPG axis as therapeutic target in various sarcoma subtypes. Although currently there are no clinical trials evaluating agents targeting heparanase and/or HSPGs in sarcomas, we here provide arguments for this strategy as potentially able to implement the therapeutic options for sarcoma patients. (C) 2016 Elsevier Ireland Ltd. All rights reserved.
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