The development of anti-angiogenic heparan sulfate oligosaccharides.
AffiliationInstitute of Cancer Sciences, Christie Hospital and University of Manchester, Withington, Manchester M20 4BX
MetadataShow full item record
AbstractAngiogenesis 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 1α (SDF-1α), which make tumours insensitive to VEGF signalling pathway inhibition. The majority of angiogenic cytokines, including VEGF-A, FGF2, IL-8 and SDF-1α, 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 Our published studies and unpublished work have demonstrated the feasibility of generating synthetic HS fragments of defined structure with biological activity against a number of angiogenic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.
CitationThe development of anti-angiogenic heparan sulfate oligosaccharides. 2014, 42 (6):1596-600 Biochem Soc Trans
JournalBiochemical Society Transactions
- Synthetic heparan sulfate oligosaccharides inhibit endothelial cell functions essential for angiogenesis.
- Authors: Cole CL, Hansen SU, Baráth M, Rushton G, Gardiner JM, Avizienyte E, Jayson GC
- Issue date: 2010 Jul 21
- Targeting tumor micro-environment for design and development of novel anti-angiogenic agents arresting tumor growth.
- Authors: Gacche RN, Meshram RJ
- Issue date: 2013 Nov
- Heparin oligosaccharides: inhibitors of the biological activity of bFGF on Caco-2 cells.
- Authors: Jayson GC, Gallagher JT
- Issue date: 1997
- Novel anti-angiogenic therapies for malignant gliomas.
- Authors: Norden AD, Drappatz J, Wen PY
- Issue date: 2008 Dec
- Endothelial heparan sulfate 6-O-sulfation levels regulate angiogenic responses of endothelial cells to fibroblast growth factor 2 and vascular endothelial growth factor.
- Authors: Ferreras C, Rushton G, Cole CL, Babur M, Telfer BA, van Kuppevelt TH, Gardiner JM, Williams KJ, Jayson GC, Avizienyte E
- Issue date: 2012 Oct 19