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
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Bevacizumab in Non Small Cell Lung Cancer: Development, Current Status and Issues
Current Medicinal Chemistry Gemini Analogs of Vitamin D
Current Topics in Medicinal Chemistry ESDA: An Improved Approach to Accurately Identify Human snoRNAs for Precision Cancer Therapy
Current Bioinformatics On the Nature of the Tumor-Initiating Cell
Current Stem Cell Research & Therapy New Developments and Prospective Applications for β (1,3) Glucans
Recent Patents on Biotechnology Ribozymes in the Age of Molecular Therapeutics
Current Molecular Medicine The Effects of Statin Therapy on the Human Airway
Drug Metabolism Letters Regulation of Mitochondrial Function and its Impact in Metabolic Stress
Current Medicinal Chemistry Small Molecule Toxins Targeting Tumor Receptors
Current Pharmaceutical Design VEGF-VEGFR System as a Target for Suppressing Inflammation and other Diseases
Endocrine, Metabolic & Immune Disorders - Drug Targets Clients and Oncogenic Roles of Molecular Chaperone gp96/grp94
Current Topics in Medicinal Chemistry Analysis of Comparative Proteomic and Potent Targets of Peniciketal A in Human Acute Monocytic Leukemia
Anti-Cancer Agents in Medicinal Chemistry RNA Interference-Based Gene Silencing in Mice: The Development of a Novel Therapeutical Strategy
Current Pharmaceutical Design Combination of Phytochemicals as Adjuvants for Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Double-Faced Role of Human Mesenchymal Stem Cells and their Role/Challenges in Cancer Therapy
Current Stem Cell Research & Therapy A Novel Method for Screening of Anti-Cancer Drugs: Availability of Screening in Acidic Medium
Recent Patents on Biomedical Engineering (Discontinued) The Potential of Statins for Individualized Colorectal Cancer Chemoprevention
Current Drug Targets Clinical Applications of the Urokinase Receptor (uPAR) for Cancer Patients
Current Pharmaceutical Design Targeting the Mevalonate Pathway for Improved Anticancer Therapy
Current Cancer Drug Targets Ticagrelor Ameliorates Bleomycin-Induced Pulmonary Fibrosis in Rats by the Inhibition of TGF-β1/Smad3 and PI3K/AKT/mTOR Pathways
Current Molecular Pharmacology