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

Research output: Contribution to journalArticle

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 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.

Details

Authors
Organisations
External organisations
  • Leiden University Medical Centre
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology

Keywords

  • Activin receptor-like kinase 1 (ALK1), Angiogenesis, Bone morphogenetic protein, Tumour vasculature
Original languageEnglish
Pages (from-to)1142-1149
Number of pages8
JournalBiochemical Society Transactions
Volume44
Issue number4
Publication statusPublished - 2016 Aug 15
Publication categoryResearch
Peer-reviewedYes

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