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The development of anti-angiogenic heparan sulfate oligosaccharides

Jayson, Gordon C.; Miller, Gavin J.; Hansen, Steen U.; Barath, Marek; Gardiner, John M.; Avizienyte, Egle


Gordon C. Jayson

Steen U. Hansen

Marek Barath

John M. Gardiner

Egle Avizienyte


Angiogenesis has emerged as a novel target for anti-cancer therapies through randomized clinical trials that tested the benefit of adding vascular endothelial growth factor (VEGF) inhibitors to conventional cytotoxic therapies. However, despite improvements in the progression-free survival, the benefit in overall survival is modest. Tumour angiogenesis is regulated by a number of angiogenic cytokines. Thus innate or acquired resistance to VEGF inhibitors can be caused, at least in part, through expression of other angiogenic cytokines, including fibroblast growth factor 2 (FGF2), interleukin 8 (IL-8) and stromal-cell-derived factor 1a (SDF-1a), which make tumours insensitive to VEGF signalling pathway inhibition. The majority of angiogenic cytokines, including VEGF-A, FGF2, IL-8 and SDF-1a, manifest an obligate dependence on heparan sulfate (HS) for their biological activity. This mandatory requirement of angiogenic cytokines for HS identifies HS as a potential target for novel anti-angiogenic therapy. Targeting multiple angiogenic cytokines with HS mimetics may represent an opportunity to inhibit tumour angiogenesis more efficiently. Our published studies and unpublished work have demonstrated the feasibility of generating synthetic HS fragments of defined structure with biological activity against a number of angiogenic cytokines.

Journal Article Type Article
Acceptance Date Dec 1, 2014
Publication Date Dec 1, 2014
Journal Biochemical Society Transactions
Print ISSN 0300-5127
Publisher Portland Press
Peer Reviewed Peer Reviewed
Volume 42
Issue 6
Pages 1596 -1600
Publisher URL