Abstract
The number of anti-angiogenic agents developed for clinical use has risen greatly over the past decade. Currently, more than 80 are in trials ranging from phase I through to phase III studies and many more are in preclinical evaluation. Much hope was envisaged for these new agents to become the panacea of anti-tumoural treatment. Unfortunately the single agent activity to date has proven to be disappointing although one trial has recently reported a survival advantage when chemotherapy was administered with anti-VEGF antibodies in the setting of advanced colorectal cancer. To an extent, this may be due to great expectations of cytostatic compounds, but recently many factors have been examined to explain the differences between clinical and experimental findings. In this review, some of the factors responsible for the discrepancy are examined, with a specific focus on inhibitors of VEGF. The key factors responsible for the lack of activity are tumour heterogeneity and redundancy in the VEGF signalling system. An increased understanding of these factors is critical to the development of effective anti-angiogenic agents and need to be taken into account as new generations of drugs emerge
Keywords: vegf, resistance, heterogeneity, signalling, redundancy, cytostatic, inhibition
Current Pharmaceutical Design
Title: Resistance to Anti-VEGF Agents
Volume: 10 Issue: 1
Author(s): Ton N. C. and Jayson G. C.
Affiliation:
Keywords: vegf, resistance, heterogeneity, signalling, redundancy, cytostatic, inhibition
Abstract: The number of anti-angiogenic agents developed for clinical use has risen greatly over the past decade. Currently, more than 80 are in trials ranging from phase I through to phase III studies and many more are in preclinical evaluation. Much hope was envisaged for these new agents to become the panacea of anti-tumoural treatment. Unfortunately the single agent activity to date has proven to be disappointing although one trial has recently reported a survival advantage when chemotherapy was administered with anti-VEGF antibodies in the setting of advanced colorectal cancer. To an extent, this may be due to great expectations of cytostatic compounds, but recently many factors have been examined to explain the differences between clinical and experimental findings. In this review, some of the factors responsible for the discrepancy are examined, with a specific focus on inhibitors of VEGF. The key factors responsible for the lack of activity are tumour heterogeneity and redundancy in the VEGF signalling system. An increased understanding of these factors is critical to the development of effective anti-angiogenic agents and need to be taken into account as new generations of drugs emerge
Export Options
About this article
Cite this article as:
C. N. Ton and C. G. Jayson, Resistance to Anti-VEGF Agents, Current Pharmaceutical Design 2004; 10 (1) . https://dx.doi.org/10.2174/1381612043453603
DOI https://dx.doi.org/10.2174/1381612043453603 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Multidisciplinary Pharmaceutical Drug Design Strategies in the Progress of Drug Discovery"
The process of developing a drug is time- and money-consuming, but also fascinating. The development of numerous computational techniques, synthetic methodologies, formulation-based drug discovery, etc. has improved the drug discovery process. The process of developing new drugs is significantly hampered by drug-poor pharmacodynamics and pharmacokinetic problems. To address these challenges, ...read more
Advances in the Molecular Pathogenesis of Inflammatory Bowel Disease.
This thematic issue will emphasize the recent breakthroughs in the mechanisms of Inflammatory bowel disease (IBD) pathogenesis and devotes some understanding of both Crohn’s and ulcerative colitis. It is expected to include studies about cellular and genetic aspects, which help to precipitate the disease, and the immune system-gut microbiome relations ...read more
Blood-based biomarkers in large-scale screening for neurodegenerative diseases
Disease biomarkers are necessary tools that can be employed in several clinical context of use (COU), ranging from the (early) diagnosis, prognosis, and prediction, to monitoring of disease state and/or drug efficacy. Regarding neurodegenerative diseases, in particular Alzheimer’s disease (AD), a battery of well-validated biomarkers are available, such as cerebrospinal ...read more
Diabetes mellitus: advances in diagnosis and treatment driving by precision medicine
Diabetes mellitus (DM) is a chronic degenerative metabolic disease with ever increasing prevalence worldwide which is now an epidemic disease affecting 500 million people worldwide. Insufficient insulin secretion from pancreatic β cells unable to maintain blood glucose homeostasis is the main feature of this disease. Multifactorial and complex nature of ...read more

- Author Guidelines
- Bentham Author Support Services (BASS)
- 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
-
Anlotinib Overcomes Multiple Drug Resistant Colorectal Cancer Cells via Inactivating PI3K/AKT Pathway
Anti-Cancer Agents in Medicinal Chemistry Pharmacogenetic Variation and Metformin Response
Current Drug Metabolism Discussion on the Structural Modification and Anti-tumor Activity of Flavonoids
Current Topics in Medicinal Chemistry Exploring Confluence-Related Signalling to Modulate the Expression of Oct4 – A Role in Facilitating Mouse Somatic Cell Reprogramming?
Current Stem Cell Research & Therapy Membrane and Soluble Forms of Endoglin in Preeclampsia
Current Molecular Medicine Blood-Brain Barrier and Breast Cancer Resistance Protein: A Limit to the Therapy of CNS Tumors and Neurodegenerative Diseases
Anti-Cancer Agents in Medicinal Chemistry New Potential Pharmaceutical Applications of Hypericum Species
Mini-Reviews in Medicinal Chemistry Modulation of k-Ras Signaling by Natural Products
Current Medicinal Chemistry Gender Effects on Rat Metabolism of AMG 900, an Orally Available Small Molecule Aurora Kinase Inhibitor
Drug Metabolism Letters From Basics of Coordination Chemistry to Understanding Cisplatin-analogue Pt Drugs
Current Pharmaceutical Design Mitochondrial Respiratory Complex I: Structure, Function and Implication in Human Diseases
Current Medicinal Chemistry Editorial (Thematic Issue: Novel Methods and Tools of the Computational Systems Biology in Bioinformatics and Biomedical Informatics)
Current Bioinformatics Fe-S Proteins Acting as Redox Switch: New Key Actors of Cellular Adaptive Responses
Current Chemical Biology Plant Coumestans: Recent Advances and Future Perspectives in Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Condensed and Hydrolysable Tannins as Antioxidants Influencing the Health
Mini-Reviews in Medicinal Chemistry The Nuclear Orphan Receptors NR4A as Therapeutic Target in Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Understanding Autophagy in Cell Death Control
Current Pharmaceutical Design NF-κB in Anti-Inflammatory Activity of Probiotics: An Update
Current Immunology Reviews (Discontinued) Old Drugs-Current Perspectives
Current Pharmacogenomics Antimicrobial, In Vitro and In Vivo Antineoplastic Activities, Mechanism of Action, Structural and Thermal Properties of a Small-Novel Pharmaceutical Organometallic Chelate
Mini-Reviews in Medicinal Chemistry