Abstract
Several cytokines and growth factors modulate angiogenesis through a fine tuned paracrine or autocrine mode of action. Among them is plateled-derived endothelial cell growth factor (PD-ECGF), which is highly is expressed in tumors, and is angiogenic by stimulation of endothelial cell migration. Studies have shown that PD-ECGF is identical to the well known enzyme thymidine phosphorylase (TP), which is involved in thymidine metabolism and homeostasis. Interestingly, PD-ECGF plays an angiogenic role as a result of its TP enzyme activity. In light of these findings, PD-ECGF/TP should not be considered a true growth factor, and its PD-ECGF name is now actually a misnomer. Recently, TP activity was thought of as an interesting potential two-face target for controling tumor-dependent angiogenesis. In fact, on one hand, its high levels of expression in tumors compared to non-neoplastic regions, and its broad substrate specificity suggested that TP could be used as an enzymatic tool to locally activate anticancer nucleoside bases or base analogs. On the other hand, its enzyme-dependent angiogenic activity engendered the search for specific inhibitors to reduce TP-dependent angiogenesis. This review will describe TP, its activity, its possible mechanisms of action and its role in angiogenesis. Particular attention will be focused on the design and biological characterization of novel TP inhibitors which recently showed promising anticancer activity.
Current Cancer Drug Targets
Title: Thymidine Phosphorylase: A Two-Face Janus in Anticancer Chemotherapy
Volume: 1 Issue: 2
Author(s): F. Focher and S. Spadari
Affiliation:
Abstract: Several cytokines and growth factors modulate angiogenesis through a fine tuned paracrine or autocrine mode of action. Among them is plateled-derived endothelial cell growth factor (PD-ECGF), which is highly is expressed in tumors, and is angiogenic by stimulation of endothelial cell migration. Studies have shown that PD-ECGF is identical to the well known enzyme thymidine phosphorylase (TP), which is involved in thymidine metabolism and homeostasis. Interestingly, PD-ECGF plays an angiogenic role as a result of its TP enzyme activity. In light of these findings, PD-ECGF/TP should not be considered a true growth factor, and its PD-ECGF name is now actually a misnomer. Recently, TP activity was thought of as an interesting potential two-face target for controling tumor-dependent angiogenesis. In fact, on one hand, its high levels of expression in tumors compared to non-neoplastic regions, and its broad substrate specificity suggested that TP could be used as an enzymatic tool to locally activate anticancer nucleoside bases or base analogs. On the other hand, its enzyme-dependent angiogenic activity engendered the search for specific inhibitors to reduce TP-dependent angiogenesis. This review will describe TP, its activity, its possible mechanisms of action and its role in angiogenesis. Particular attention will be focused on the design and biological characterization of novel TP inhibitors which recently showed promising anticancer activity.
Export Options
About this article
Cite this article as:
Focher F. and Spadari S., Thymidine Phosphorylase: A Two-Face Janus in Anticancer Chemotherapy, Current Cancer Drug Targets 2001; 1 (2) . https://dx.doi.org/10.2174/1568009013334232
DOI https://dx.doi.org/10.2174/1568009013334232 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Visfatin: Structure, Function and Relation to Diabetes Mellitus and Other Dysfunctions
Current Medicinal Chemistry Current Breakthroughs in Structure-based Design of Synthetic and Natural Sourced Inhibitors Against Zika Viral Targets
Current Topics in Medicinal Chemistry Antibody Engineering for Targeted Therapy of Cancer Recombinant Fv-Immunotoxins
Current Pharmaceutical Biotechnology Kinase Inhibitors in Multitargeted Cancer Therapy
Current Medicinal Chemistry Pharmacogenetics of Therapy in Inflammatory Bowel Disease Patients
Current Pharmacogenomics Therapeutic Nucleic Acids
Recent Patents on Regenerative Medicine Onconase and Amphinase, the Antitumor Ribonucleases from Rana pipiens Oocytes
Current Pharmaceutical Biotechnology Potential Role of PKC Inhibitors in the Treatment of Hematological Malignancies
Current Pharmaceutical Design The Inhibitory Co-Receptors: A Way to Save from Anergy the HIVSpecific T Cells
Current HIV Research Recent Patents Relating to siRNAs and Therapeutic Strategies for Genetic Diseases
Recent Patents on DNA & Gene Sequences Hydroxychloroquine Sulfate (Plaquenil): A Possible Candidate for Pandemic SARS-CoV-2 or (COVID-19) ?
Coronaviruses B Cells Compartment in Centenarian Offspring and Old People
Current Pharmaceutical Design A Glycation Angle to Look into the Diabetic Vasculopathy: Cause and Cure
Current Vascular Pharmacology Hypoxia and Oxidative Stress in the Causation of Diabetic Retinopathy
Current Diabetes Reviews The Relationship Between Social Support, Social Constraint, and Psychological Adjustment for Patients with Rare Autoimmune Disease
Current Rheumatology Reviews The Interaction Between Gender and Diabetes Mellitus in the Coronary Heart Disease Risk
Current Pharmaceutical Design Meet the Editor
Reviews on Recent Clinical Trials Dysglycemia and Abdominal Obesity
Current Vascular Pharmacology The Effects of Obesity on the Cerebral Vasculature
Current Vascular Pharmacology Conditional Cardiac Overexpression of S100A6 Attenuates Myocyte Hypertrophy and Apoptosis Following Myocardial Infarction
Current Pharmaceutical Design