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Targeting tumour vasculature by inhibiting activin receptor-like kinase (ALK)1 function

De Vinuesa, Amaya García; Bocci, Matteo LU ; Pietras, Kristian LU and Dijke, Peter Ten (2016) In Biochemical Society Transactions 44(4). p.1142-1149
Abstract

Angiogenesis is a hallmark of cancer and is now a validated therapeutic target in the clinical setting. Despite the initial success, anti-angiogenic compounds impinging on the vascular endothelial growth factor (VEGF) pathway display limited survival benefits in patients and resistance often develops due to activation of alternative pathways. Thus, finding and validating new targets is highly warranted. Activin receptor-like kinase (ALK)1 is a transforming growth factor beta (TGF-β) type I receptor predominantly expressed in actively proliferating endothelial cells (ECs). ALK1 has been shown to play a pivotal role in regulating angiogenesis by binding to bone morphogenetic protein (BMP)9 and 10. Two main pharmacological inhibitors, an... (More)

Angiogenesis is a hallmark of cancer and is now a validated therapeutic target in the clinical setting. Despite the initial success, anti-angiogenic compounds impinging on the vascular endothelial growth factor (VEGF) pathway display limited survival benefits in patients and resistance often develops due to activation of alternative pathways. Thus, finding and validating new targets is highly warranted. Activin receptor-like kinase (ALK)1 is a transforming growth factor beta (TGF-β) type I receptor predominantly expressed in actively proliferating endothelial cells (ECs). ALK1 has been shown to play a pivotal role in regulating angiogenesis by binding to bone morphogenetic protein (BMP)9 and 10. Two main pharmacological inhibitors, an ALK1-Fc fusion protein (Dalantercept/ACE-041) and a fully human antibody against the extracellular domain of ALK1 (PF-03446962) are currently under clinical development. Herein, we briefly recapitulate the role of ALK1 in blood vessel formation and the current status of the preclinical and clinical studies on inhibition of ALK1 signalling as an anti-angiogenic strategy. Future directions in terms of new combination regimens will also be presented.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Activin receptor-like kinase 1 (ALK1), Angiogenesis, Bone morphogenetic protein, Tumour vasculature
in
Biochemical Society Transactions
volume
44
issue
4
pages
8 pages
publisher
Biochemical Society
external identifiers
  • scopus:85009818989
  • wos:000392728300022
ISSN
0300-5127
DOI
10.1042/BST20160093
language
English
LU publication?
yes
id
42bcdea0-b4d5-44e1-baeb-a3e0b06c5a94
date added to LUP
2017-04-13 09:43:55
date last changed
2017-10-22 05:29:19
@article{42bcdea0-b4d5-44e1-baeb-a3e0b06c5a94,
  abstract     = {<p>Angiogenesis is a hallmark of cancer and is now a validated therapeutic target in the clinical setting. Despite the initial success, anti-angiogenic compounds impinging on the vascular endothelial growth factor (VEGF) pathway display limited survival benefits in patients and resistance often develops due to activation of alternative pathways. Thus, finding and validating new targets is highly warranted. Activin receptor-like kinase (ALK)1 is a transforming growth factor beta (TGF-β) type I receptor predominantly expressed in actively proliferating endothelial cells (ECs). ALK1 has been shown to play a pivotal role in regulating angiogenesis by binding to bone morphogenetic protein (BMP)9 and 10. Two main pharmacological inhibitors, an ALK1-Fc fusion protein (Dalantercept/ACE-041) and a fully human antibody against the extracellular domain of ALK1 (PF-03446962) are currently under clinical development. Herein, we briefly recapitulate the role of ALK1 in blood vessel formation and the current status of the preclinical and clinical studies on inhibition of ALK1 signalling as an anti-angiogenic strategy. Future directions in terms of new combination regimens will also be presented.</p>},
  author       = {De Vinuesa, Amaya García and Bocci, Matteo and Pietras, Kristian and Dijke, Peter Ten},
  issn         = {0300-5127},
  keyword      = {Activin receptor-like kinase 1 (ALK1),Angiogenesis,Bone morphogenetic protein,Tumour vasculature},
  language     = {eng},
  month        = {08},
  number       = {4},
  pages        = {1142--1149},
  publisher    = {Biochemical Society},
  series       = {Biochemical Society Transactions},
  title        = {Targeting tumour vasculature by inhibiting activin receptor-like kinase (ALK)1 function},
  url          = {http://dx.doi.org/10.1042/BST20160093},
  volume       = {44},
  year         = {2016},
}