title: Activin receptor inhibitors--dalantercept.
abstract: Development of anti-angiogenic therapy including the vascular endothelial growth factor (VEGF) antibodies and VEGF-tyrosine kinase receptors has been a major landmark in cancer therapy leading improvement in survival in several cancers. While anti-angiogenic therapy is effective in some settings, resistance often develops owing to evasive, alternative pathways. Novel targets for anti-angiogenic therapy are urgently required to provide treatment alternatives in patients whose tumors are unresponsive to approved anti-angiogenic agents; one such pathway is the bone morphogenetic proteins (BMP 9 and BMP 10) that activate the type I activin receptor-like kinase-1 (ALK1), which has been implicated in the development of functional vasculature. Dalantercept (ACE-041) is a novel anti-angiogenic agent, which is a soluble form of ALK1, and acts as a ligand trap for BMP 9 and BMP 10, inhibiting their interaction with ALK1, which further disrupts the process of vascular development. This review will discuss the preclinical and clinical development of dalantercept as a novel anti-angiogenic therapy in treating a variety of cancers and its distinct safety profile compared to other anti-VEGF agents. We will also discuss the ongoing and completed studies of dalantercept, including combination studies with other VEGF-directed therapies.
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA, Shilpa.Gupta@moffitt.org.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Gupta
authors.forename: David
authors.initials: D
authors.lastname: Gill
authors.forename: Sumanta K
authors.initials: SK
authors.lastname: Pal
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
mesh_terms: D030301:Activin Receptors, Type II / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D019485:Bone Morphogenetic Proteins / Q000187:drug effects / Q000378:metabolism*; D002986:Clinical Trials as Topic; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors / Q000378:metabolism; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000494:pharmacology*; D009369:Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; C541386:BMP10 protein, human; D019485:Bone Morphogenetic Proteins; C525887:GDF2 protein, human; D055427:Growth Differentiation Factor 2; D055412:Growth Differentiation Factors; D007141:Immunoglobulin Fc Fragments; D011993:Recombinant Fusion Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II; C000591618:ALK1-Fc fusion protein, human