Gordon C. Jayson
The development of anti-angiogenic heparan sulfate oligosaccharides
Jayson, Gordon C.; Miller, Gavin J.; Hansen, Steen U.; Barath, Marek; Gardiner, John M.; Avizienyte, Egle
Authors
Abstract
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 Our published studies and unpublished work have demonstrated the feasibility of generating synthetic HS fragments of defined structure with biological activity against a number of angiogenic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.
Citation
Jayson, G. C., Miller, G. J., Hansen, S. U., Barath, M., Gardiner, J. M., & Avizienyte, E. (2014). The development of anti-angiogenic heparan sulfate oligosaccharides. Biochemical Society Transactions, 42(6), 1596 -1600. https://doi.org/10.1042/BST20140229
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 |
DOI | https://doi.org/10.1042/BST20140229 |
Publisher URL | https://doi.org/10.1042/bst20140229 |
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