Abstract
Angiogenesis is important in the growth and progression of solid tumours. The main pro-angiogenic factor, namely vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a potent angiogenic cytokine that induces mitosis and also regulates the permeability of endothelial cells. The soluble isoform of VEGF is a dimeric glycoprotein of 36-46 kDa, induced by hypoxia and oncogenic mutation and it binds to two specific tyrosinekinase receptors: VEGF-1 (flt-1) and VEGF-2 (KDR/flk1). An increase in VEGF expression in tumour tissue or some blood compartments (i.e. serum or plasma) has been found in solid and haematological malignancies of various origins and is associated with metastasis formation and poor prognosis. Bevacizumab, a recombinant humanised monoclonal antibody developed against VEGF, binds to soluble VEGF, preventing receptor binding and inhibiting endothelial cell proliferation and vessel formation. Pre-clinical and clinical studies have shown that bevacizumab alone or in combination with a cytotoxic agent decreases tumour growth and increases median survival time and time to tumour progression. Bevacizumab is the first anti-angiogenetic treatment approved by the American Food and Drug Administration in the first-line treatment of metastatic colorectal cancer. It has shown preliminary evidence of efficacy for breast, non-small-cell lung, pancreatic, prostate, head and neck and renal cancer as well as haematological malignancies. Common toxicities associated with bevacizumab include hypertension, proteinuria, bleeding episodes and thrombotic events. This review summarises the critical role of VEGF and discusses the data available on bevacizumab, from the humanisation of its parent murine monoclonal antibody (mAb) A.4.6.1 to its use in cancer clinical trials.
Keywords: Angiogenesis, VEGF, angiogenesis inhibitor, monoclonal antibodies targeting VEGF, bevacizumab, pre-clinical studies, clinical trials, cancer
Current Medicinal Chemistry
Title: Vascular Endothelial Growth Factor (VEGF) as a Target of Bevacizumab in Cancer: From the Biology to the Clinic
Volume: 13 Issue: 16
Author(s): Girolamo Ranieri, Rosa Patruno, Eustachio Ruggieri, Severino Montemurro, Paolo Valerio and Domenico Ribatti
Affiliation:
Keywords: Angiogenesis, VEGF, angiogenesis inhibitor, monoclonal antibodies targeting VEGF, bevacizumab, pre-clinical studies, clinical trials, cancer
Abstract: Angiogenesis is important in the growth and progression of solid tumours. The main pro-angiogenic factor, namely vascular endothelial growth factor (VEGF), also known as vascular permeability factor, is a potent angiogenic cytokine that induces mitosis and also regulates the permeability of endothelial cells. The soluble isoform of VEGF is a dimeric glycoprotein of 36-46 kDa, induced by hypoxia and oncogenic mutation and it binds to two specific tyrosinekinase receptors: VEGF-1 (flt-1) and VEGF-2 (KDR/flk1). An increase in VEGF expression in tumour tissue or some blood compartments (i.e. serum or plasma) has been found in solid and haematological malignancies of various origins and is associated with metastasis formation and poor prognosis. Bevacizumab, a recombinant humanised monoclonal antibody developed against VEGF, binds to soluble VEGF, preventing receptor binding and inhibiting endothelial cell proliferation and vessel formation. Pre-clinical and clinical studies have shown that bevacizumab alone or in combination with a cytotoxic agent decreases tumour growth and increases median survival time and time to tumour progression. Bevacizumab is the first anti-angiogenetic treatment approved by the American Food and Drug Administration in the first-line treatment of metastatic colorectal cancer. It has shown preliminary evidence of efficacy for breast, non-small-cell lung, pancreatic, prostate, head and neck and renal cancer as well as haematological malignancies. Common toxicities associated with bevacizumab include hypertension, proteinuria, bleeding episodes and thrombotic events. This review summarises the critical role of VEGF and discusses the data available on bevacizumab, from the humanisation of its parent murine monoclonal antibody (mAb) A.4.6.1 to its use in cancer clinical trials.
Export Options
About this article
Cite this article as:
Ranieri Girolamo, Patruno Rosa, Ruggieri Eustachio, Montemurro Severino, Valerio Paolo and Ribatti Domenico, Vascular Endothelial Growth Factor (VEGF) as a Target of Bevacizumab in Cancer: From the Biology to the Clinic, Current Medicinal Chemistry 2006; 13 (16) . https://dx.doi.org/10.2174/092986706777585059
DOI https://dx.doi.org/10.2174/092986706777585059 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Approaches to the treatment of chronic inflammation
Chronic inflammation is a hallmark of numerous diseases, significantly impacting global health. Although chronic inflammation is a hot topic, not much has been written about approaches to its treatment. This thematic issue aims to showcase the latest advancements in chronic inflammation treatment and foster discussion on future directions in this ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...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
- Announcements
Related Articles
-
Safety and Efficacy of Novel Oral Anticoagulants: A Comparison to Vitamin K Antagonists
Cardiovascular & Hematological Agents in Medicinal Chemistry Patent Annotations
Recent Patents on Cardiovascular Drug Discovery Safety of Dabigatran in an Elderly Population: Single Center Experience in Italy
Current Drug Safety Cardiovascular Risk in Patients with Primary Hyperparathyroidism
Current Pharmaceutical Design Herbal and Traditional Chinese Medicine for the Treatment of Cardiovascular Complications in Diabetes Mellitus
Current Diabetes Reviews Adiponectin as a Regulator of Vascular Redox State: Therapeutic Implications
Recent Patents on Cardiovascular Drug Discovery Selective Estrogen Receptor Modulators and Aromatase Inhibitors for Breast Cancer Chemoprevention
Current Drug Targets Stem Cells Transplantation in the Treatment of Patients with Liver Failure
Current Stem Cell Research & Therapy Nitric Oxide and Cyclic GMP Signaling Pathway as a Focus for Drug Development
Current Medicinal Chemistry Chronic Hyperuricemia, Uric Acid Deposit and Cardiovascular Risk
Current Pharmaceutical Design Obesity and Body Fat Distribution as Predictors for Obstructive Sleep Apnea Syndrome
Current Respiratory Medicine Reviews Mesenchymal Stem Cell-derived Extracellular Vesicles for Renal Repair
Current Gene Therapy Cardiac Remodeling and Exercise Training in Hypertension
Current Hypertension Reviews Determination of Bioactive Constituents in Traditional Chinese Medicines by CE with Electrochemical Detection
Current Medicinal Chemistry Genetics of Atrial Fibrilation: In Search of Novel Therapeutic Targets
Cardiovascular & Hematological Disorders-Drug Targets Human Urotensin II and Metabolic Syndrome
Vascular Disease Prevention (Discontinued) Anti-Angiogenic Therapies for Children with Cancer
Current Cancer Drug Targets Radiological Presentation of H1N1 Influenza in the 2017 Outbreak in India and Correlation with Patient Outcome
Current Respiratory Medicine Reviews Clinical Pharmacotherapy and Drug Development for Pulmonary Arterial Hypertension
Recent Patents on Cardiovascular Drug Discovery Editorial [Herbal Remedies in Pulmonary Medicine: A Word of Caution]
Current Respiratory Medicine Reviews