Abstract
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.
Mini-Reviews in Medicinal Chemistry
Title:Activin Receptor-Like Kinase 1: a Novel Anti-angiogenesis Target from TGF-β Family
Volume: 13 Issue: 10
Author(s): Luca Vecchia, Carla Olivieri and Claudia Scotti
Affiliation:
Keywords: ACVRL1, ALK1, Activin Receptor-like Kinase 1, angiogenesis, cancer, antibodies, biologics.
Abstract: 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.
Export Options
About this article
Cite this article as:
Vecchia Luca, Olivieri Carla and Scotti Claudia, Activin Receptor-Like Kinase 1: a Novel Anti-angiogenesis Target from TGF-β Family, Mini-Reviews in Medicinal Chemistry 2013; 13 (10) . https://dx.doi.org/10.2174/13895575113139990065
DOI https://dx.doi.org/10.2174/13895575113139990065 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
Call for Papers in Thematic Issues
Bioprospecting of Natural Products as Sources of New Multitarget Therapies
According to the Convention on Biological Diversity, bioprospecting is the exploration of biodiversity and indigenous knowledge to develop commercially valuable products for pharmaceutical and other applications. Bioprospecting involves searching for useful organic compounds in plants, fungi, marine organisms, and microorganisms. Natural products traditionally constituted the primary source of more than ...read more
Computational Frontiers in Medicinal Chemistry
The thematic issue "Computational Frontiers in Medicinal Chemistry" provides a robust platform for delving into state-of-the-art computational methodologies and technologies that significantly propel advancements in medicinal chemistry. This edition seeks to amalgamate top-tier reviews spotlighting the latest trends and breakthroughs in the fusion of computational approaches, including artificial intelligence (AI) ...read more
Natural Products and Dietary Supplements in Alleviation of Metabolic, Cardiovascular, and Neurological Disorders
Metabolic disorders like diabetes, obesity, inflammation, oxidative stress, cancer etc, cardiovascular disorders like angina, myocardial infarction, congestive heart failure etc as well as neurological disorders like Alzheimer?s, Parkinson?s, Epilepsy, Depression, etc are the global burden. They covered the major segment of the diseases and disorders from which the human community ...read more
Natural Products in Drug Discovery
Natural products have always been one of the important ways of drug discovery due to their novel skeleton and diverse functional group characteristics. According to statistics, between 1981 and 2019, the FDA approved a total of 1,394 small molecule drugs for marketing, of which 930 marketed drugs originated from the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Mechanisms of Melatonin in Alleviating Alzheimer’s Disease
Current Neuropharmacology ES-MDA: Enhanced Similarity-based MiRNA-Disease Association
Current Protein & Peptide Science Current Prevention and Treatment of Postoperative Nausea and Vomiting after Gynecological Laparoscopic Surgery
Current Drug Therapy Biology and Therapeutic Applications of Peroxisome Proliferator- Activated Receptors
Current Topics in Medicinal Chemistry Editorial (Hot Topic: Translational Medicine is Promoting Cross-talk of Interdiscipline)
Anti-Cancer Agents in Medicinal Chemistry Stress, Depression and Hippocampal Apoptosis
CNS & Neurological Disorders - Drug Targets Promotion of Insulin-Like Growth Factor-I Production by Sensory Neuron Stimulation; Molecular Mechanism(s) and Therapeutic Implications
Current Medicinal Chemistry Retraction Notice: Current Management of Vomiting After Tonsillectomy in Children
Current Drug Safety The Impact of Inflammatory Bowel Disease (IBD) and its Treatment on the Reproductive Process
Current Women`s Health Reviews A Novel Treatment Strategy for Sepsis and Septic Shock Based on the Interactions between Prostanoids, Nitric Oxide, and 20-Hydroxyeicosatetraenoic Acid
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Natural Products as Aromatase Inhibitors
Anti-Cancer Agents in Medicinal Chemistry Recent Advances and Challenges in Steroid Metabolomics for Biomarker Discovery
Current Medicinal Chemistry Inflammatory and Neurodegenerative Pathways in Depression: A New Avenue for Antidepressant Development?
Current Medicinal Chemistry Systemic Redox Biomarkers in Neurodegenerative Diseases
Current Drug Metabolism Thyroid Hormone Modulation of Immunity: Its Participation in Chronic Stress-Induced Immune Alterations
Current Immunology Reviews (Discontinued) MGMT Epigenetics: The Influence of Gene Body Methylation and Other Insights Derived from Integrated Methylomic, Transcriptomic, and Chromatin Analyses in Various Cancer Types
Current Cancer Drug Targets HIF-1α Modulates Energy Metabolism in Cancer Cells by Inducing Over-Expression of Specific Glycolytic Isoforms
Mini-Reviews in Medicinal Chemistry The Urokinase Plasminogen Activator System: A Target for Anti-Cancer Therapy
Current Cancer Drug Targets Is Intake of Flavonoid-Based Food Supplements During Pregnancy Safe for the Developing Child? A Literature Review
Current Drug Targets Vasopressin in Health and Disease with a Focus on Affective Disorders
Central Nervous System Agents in Medicinal Chemistry