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

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

Expert Opin Investig Drugs

Leiden 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 ;

Published: November 2013

AI Article Synopsis

Article Abstract

Introduction: Formation of blood vessels from pre-existing ones, also termed angiogenesis, is of crucial importance for the outgrowth of tumours beyond 1 - 2 mm³. Therefore, anti-angiogenic therapies, mainly focussing on inhibition of vascular endothelial growth factor (VEGF) are used in clinical therapy. However, although initially reducing tumour size, therapy resistance occurs frequently and new targets are needed. A possible target is activin receptor-like kinase (ALK)-1, a transforming growth factor (TGF)-β type-I receptor, which binds bone morphogenetic protein (BMP)-9 and -10 with high affinity and has an important role in regulating angiogenesis.

Areas Covered: Several approaches to interfere with ALK1 signalling have been developed, that is, ALK1 neutralising antibodies and a soluble ALK1 extracellular domain/Fc fusion protein (ALK1-Fc), acting as a ligand trap. In this review, we discuss the involvement of ALK1 in angiogenesis, in a variety of diseases and the current status of the development of ALK1 inhibitors for cancer therapy.

Expert Opinion: Based on current, mainly preclinical studies on inhibition of ALK1 signalling by ligand traps and neutralising antibodies, targeting ALK1 seems very promising. Both ALK1-Fc and neutralising antibodies strongly inhibit angiogenesis in vitro and in vivo. The results from the first Phase I clinical trials are to be reported soon and multiple Phase II studies are ongoing.

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Source
http://dx.doi.org/10.1517/13543784.2013.837884DOI Listing

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