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

Author:
  • Amaya García De Vinuesa
  • Matteo Bocci
  • Kristian Pietras
  • Peter Ten Dijke
Publishing year: 2016-08-15
Language: English
Pages: 1142-1149
Publication/Series: Biochemical Society Transactions
Volume: 44
Issue: 4
Document type: Journal article
Publisher: Biochemical Society

Abstract english

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.

Keywords

  • Cancer and Oncology
  • Activin receptor-like kinase 1 (ALK1)
  • Angiogenesis
  • Bone morphogenetic protein
  • Tumour vasculature

Other

Published
  • ISSN: 0300-5127
Kristian Pietras
E-mail: kristian [dot] pietras [at] med [dot] lu [dot] se

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Division of Translational Cancer Research

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Experimental oncology