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Activin receptor-like kinase 1 as a target for anti-angiogenesis therapy

Lukas Jac Hawinkels1, Amaya Garcia de Vinuesa, Peter Ten Dijke

  • 1Leiden University Medical Centre, Cancer Genomics Centre Netherlands and Centre for BioMedical Genetics, Department of Molecular Cell Biology , Building-2, S1-P, PO box 9600, 2300 RC Leiden , The Netherlands +31 71 526 9272 ; +31 71 526 8270 ; L.J.A.C.Hawinkels@LUMC.nl.

Expert Opinion on Investigational Drugs
|September 24, 2013
PubMed
Abstract

Insights

Targeting activin receptor-like kinase (ALK)-1 shows promise for cancer therapy by inhibiting angiogenesis. ALK1 inhibitors, including ALK1-Fc and neutralizing antibodies, demonstrate significant potential in preclinical studies, with clinical trials underway.

Area of Science:

  • Oncology
  • Vascular Biology
  • Drug Development

Background:

  • Tumor growth beyond 1-2 mm³ relies on angiogenesis, the formation of new blood vessels.
  • Current anti-angiogenic therapies targeting vascular endothelial growth factor (VEGF) often face therapy resistance.
  • Activin receptor-like kinase (ALK)-1, a TGF-β type-I receptor binding BMP-9 and BMP-10, is a potential therapeutic target due to its role in angiogenesis.

Purpose of the Study:

  • To review the involvement of ALK1 in angiogenesis and various diseases.
  • To discuss the current status of ALK1 inhibitors for cancer therapy.

Main Methods:

  • Development of ALK1 neutralising antibodies.
  • Development of a soluble ALK1 extracellular domain/Fc fusion protein (ALK1-Fc) as a ligand trap.

Main Results:

  • ALK1 inhibition via ligand traps and neutralizing antibodies shows significant promise based on preclinical studies.
  • Both ALK1-Fc and neutralizing antibodies effectively inhibit angiogenesis in vitro and in vivo.
  • Early clinical trial results are anticipated, with multiple Phase II studies in progress.

Conclusions:

  • Targeting ALK1 signaling represents a promising strategy for cancer therapy.
  • ALK1 inhibitors have demonstrated potent anti-angiogenic effects.
  • Ongoing clinical trials will further elucidate the therapeutic potential of ALK1 inhibition.

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