Anti-angiogenic therapy represents a very promising approach in cancer treatment, as most tumors needs to be
supplied by a functional vascular network in order to grow beyond the local boundaries and metastatize. The accessibility
of vessels to drug delivery and the broad spectrum of cancers treatable with the same compound have arisen interest in
research of suitable molecules, with several, especially targeting the VEGF pathway, entered in clinical trials and
approved by the Food and Drug Administration. Despite good results, the major hurdle resides in the limited duration of
an effective clinical response before tumors start to grow again. Thus, researchers are looking for different alternative
targets for a combined and parallel multi-targeting of angiogenic signaling circuits. Activin Receptor-like kinase 1
(ALK1) is a TGF-β type I receptor with high affinity for the BMP9 member of Bone Morphogenic Proteins superfamily:
it is expressed mainly, even if not exclusively, on endothelial cells and seems to be involved in the regulatory phase of
angiogenesis. Despite a non-completely elucidated mechanism, the targeting of this pathway, both by a soluble ALK1-Fc
receptor developed by Acceleron Pharma and by a fully human monoclonal antibody developed by Pfizer, has achieved
encouraging results. After having briefly summarized the state of the art of anti-angiogenic therapy, we will first review
existing evidence about the molecular mechanisms of ALK1 signaling and we will then analyse in detail the pre-clinical
and clinical data available about these two drugs.
Keywords: ACVRL1, ALK1, Activin Receptor-like Kinase 1, angiogenesis, cancer, antibodies, biologics.
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