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Kristian Pietras

Kristian Pietras

Research team manager

Kristian Pietras

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

Author

  • Amaya García De Vinuesa
  • Matteo Bocci
  • Kristian Pietras
  • Peter Ten Dijke

Summary, in 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.

Department/s

  • Department of Laboratory Medicine
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation

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

Topic

  • Cancer and Oncology

Keywords

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

Status

Published

ISBN/ISSN/Other

  • ISSN: 0300-5127