The clinical potential of antiangiogenic fragments of extracellular matrix proteins.

2.50
Hdl Handle:
http://hdl.handle.net/10541/74933
Title:
The clinical potential of antiangiogenic fragments of extracellular matrix proteins.
Authors:
Clamp, Andrew R; Jayson, Gordon C ( 0000-0002-8515-8944 )
Abstract:
Neovasculature development is a crucial step in the natural history of a cancer. While much emphasis has been placed on proangiogenic growth factors such as VEGF, it is clear that endogenous angiogenesis inhibitors also have critical roles in the regulation of this process. Recent research has identified several cryptic fragments of extracellular matrix/vascular basement membrane proteins that have potent antiangiogenic properties in vivo. It has become apparent that many of these fragments signal via interactions with endothelial integrins, although multiple downstream effector pathways have been implicated and endostatin, the first non-collagenous domain of collagen XVIII, influences an intricate signalling network. The activity of these molecules in animal models suggests that they may have significant clinical activity; however, results of phase I/II trials with endostatin were disappointing. Many possible reasons can be found for the failure of these studies. Weaknesses in trial design, endostatin administration regimen and patient selection are identifiable, and importantly the lack of a clearly defined antiangiogenic mechanism for endostatin hindered assessment of biologically effective dose. Additionally, in vivo immunological and proteolytic function-neutralising mechanisms may have negated endostatin's actions. Lessons learned from these studies will aid the future clinical development of other antiangiogenic extracellular matrix protein fragments.
Affiliation:
Cancer Research UK Department of Medical Oncology, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK. aclamp@picr.man.ac.uk
Citation:
The clinical potential of antiangiogenic fragments of extracellular matrix proteins. 2005, 93 (9):967-72 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
31-Oct-2005
URI:
http://hdl.handle.net/10541/74933
DOI:
10.1038/sj.bjc.6602820
PubMed ID:
16234821
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorClamp, Andrew R-
dc.contributor.authorJayson, Gordon C-
dc.date.accessioned2009-07-22T10:47:10Z-
dc.date.available2009-07-22T10:47:10Z-
dc.date.issued2005-10-31-
dc.identifier.citationThe clinical potential of antiangiogenic fragments of extracellular matrix proteins. 2005, 93 (9):967-72 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid16234821-
dc.identifier.doi10.1038/sj.bjc.6602820-
dc.identifier.urihttp://hdl.handle.net/10541/74933-
dc.description.abstractNeovasculature development is a crucial step in the natural history of a cancer. While much emphasis has been placed on proangiogenic growth factors such as VEGF, it is clear that endogenous angiogenesis inhibitors also have critical roles in the regulation of this process. Recent research has identified several cryptic fragments of extracellular matrix/vascular basement membrane proteins that have potent antiangiogenic properties in vivo. It has become apparent that many of these fragments signal via interactions with endothelial integrins, although multiple downstream effector pathways have been implicated and endostatin, the first non-collagenous domain of collagen XVIII, influences an intricate signalling network. The activity of these molecules in animal models suggests that they may have significant clinical activity; however, results of phase I/II trials with endostatin were disappointing. Many possible reasons can be found for the failure of these studies. Weaknesses in trial design, endostatin administration regimen and patient selection are identifiable, and importantly the lack of a clearly defined antiangiogenic mechanism for endostatin hindered assessment of biologically effective dose. Additionally, in vivo immunological and proteolytic function-neutralising mechanisms may have negated endostatin's actions. Lessons learned from these studies will aid the future clinical development of other antiangiogenic extracellular matrix protein fragments.en
dc.language.isoenen
dc.subjectCanceren
dc.subject.meshAngiogenesis Inhibitors-
dc.subject.meshAnimals-
dc.subject.meshCollagen Type XVIII-
dc.subject.meshEndostatins-
dc.subject.meshExtracellular Matrix Proteins-
dc.subject.meshHumans-
dc.subject.meshNeoplasms-
dc.subject.meshNeovascularization, Pathologic-
dc.subject.meshPeptide Fragments-
dc.subject.meshVascular Endothelial Growth Factor A-
dc.titleThe clinical potential of antiangiogenic fragments of extracellular matrix proteins.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK Department of Medical Oncology, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK. aclamp@picr.man.ac.uken
dc.identifier.journalBritish Journal of Canceren

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