Abstract
The cytochrome P450s are an essential group of enzymes involved in metabolism of drugs, foreign chemicals, arachidonic acid, cholesterol, steroids and other important lipids. The cytochrome P450 enzyme system is responsible for much of the phase I metabolism of chemotherapeutic agents. At the simplest level the detoxification properties of the cytochrome P450s are used to help clear a cytotoxic before it results in serious irreversible toxicity to the patient while at other levels the cytochrome P450s are involved to varying extents in drug bioactivation. This metabolism primarily occurs in organs and tissues of the body known to express cytochrome P450 ubiquitously (i.e. liver and gastrointestinal tract), but there is also evidence to suggest that it occurs within the tumor microenvironment due to localized, tumor specific expression of certain P450 isoforms. Several of todays currently prescribed cytotoxics (e.g. cyclophosphamide and tamoxifen) undergo systematic bioactivation by cytochrome P450, which often results in toxicity to the patient. The realization that many tumors have differential cytochrome P450 expression when compared to the corresponding normal tissue has allowed the rational design of the next generation of cytotoxic around cytochrome P450 enzymology. Several new agents now entering clinical trials (e.g. Phortress and AQ4N) are specifically designed to exploit tumor cytochrome P450, resulting in local bioactivation of the cytotoxic at the tumor site. Specific activation of pro-drugs by isoforms whose expression or particular catalytic activity is limited to cancer cells offers the possibility of truly targeted chemotherapy with minimized systemic toxicity.
Keywords: cytochrome p450, cytotoxic bioactivation, cytotoxics, cyclophosphamide, tamoxifen
Current Cancer Drug Targets
Title: The Role of Cytochrome P450 in Cytotoxic Bioactivation: Future Therapeutic Directions
Volume: 4 Issue: 3
Author(s): P. H. Rooney, C. Telfer, M. C. E. McFadyen, W. T. Melvin and G. I. Murray
Affiliation:
Keywords: cytochrome p450, cytotoxic bioactivation, cytotoxics, cyclophosphamide, tamoxifen
Abstract: The cytochrome P450s are an essential group of enzymes involved in metabolism of drugs, foreign chemicals, arachidonic acid, cholesterol, steroids and other important lipids. The cytochrome P450 enzyme system is responsible for much of the phase I metabolism of chemotherapeutic agents. At the simplest level the detoxification properties of the cytochrome P450s are used to help clear a cytotoxic before it results in serious irreversible toxicity to the patient while at other levels the cytochrome P450s are involved to varying extents in drug bioactivation. This metabolism primarily occurs in organs and tissues of the body known to express cytochrome P450 ubiquitously (i.e. liver and gastrointestinal tract), but there is also evidence to suggest that it occurs within the tumor microenvironment due to localized, tumor specific expression of certain P450 isoforms. Several of todays currently prescribed cytotoxics (e.g. cyclophosphamide and tamoxifen) undergo systematic bioactivation by cytochrome P450, which often results in toxicity to the patient. The realization that many tumors have differential cytochrome P450 expression when compared to the corresponding normal tissue has allowed the rational design of the next generation of cytotoxic around cytochrome P450 enzymology. Several new agents now entering clinical trials (e.g. Phortress and AQ4N) are specifically designed to exploit tumor cytochrome P450, resulting in local bioactivation of the cytotoxic at the tumor site. Specific activation of pro-drugs by isoforms whose expression or particular catalytic activity is limited to cancer cells offers the possibility of truly targeted chemotherapy with minimized systemic toxicity.
Export Options
About this article
Cite this article as:
Rooney H. P., Telfer C., E. McFadyen C. M., Melvin T. W. and Murray I. G., The Role of Cytochrome P450 in Cytotoxic Bioactivation: Future Therapeutic Directions, Current Cancer Drug Targets 2004; 4 (3) . https://dx.doi.org/10.2174/1568009043333014
DOI https://dx.doi.org/10.2174/1568009043333014 |
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
-
Phosphorothioate Oligonucleotides: Effectiveness and Toxicity
Current Drug Targets Combined Effect of Parthenolide and Various Anti-cancer Drugs or Anticancer Candidate Substances on Malignant Cells in vitro and in vivo
Mini-Reviews in Medicinal Chemistry Inflammation-Mediating Proteases: Structure, Function in (Patho) Physiology and Inhibition
Protein & Peptide Letters Pleiotropic Effects of Cardioactive Glycosides
Current Medicinal Chemistry Imatinib Mesylate for the Treatment of Solid Tumours: Recent Trials and Future Directions
Current Enzyme Inhibition Selective VEGFR Inhibitors for Anticancer Therapeutics in Clinical Use and Clinical Trials
Current Pharmaceutical Design Anticancer Properties of Amino Acid and Peptide Derivatives of Mycophenolic Acid
Anti-Cancer Agents in Medicinal Chemistry Action of Nanoparticles on Platelet Activation and Plasmatic Coagulation
Current Medicinal Chemistry Current Status and Future Prospects of C1 Domain Ligands as Drug Candidates
Current Topics in Medicinal Chemistry Heat Shock Protein (HSP) Drug Discovery and Development: Targeting Heat Shock Proteins in Disease
Current Topics in Medicinal Chemistry Non Steroidal Anti Inflammatory Drugs As Gatekeepers Of Colon Carcinoma Highlight New Scenarios Beyond Cyclooxygenases Inhibition
Current Cancer Drug Targets The Use of Therapeutic Peptides to Target and to Kill Cancer Cells
Current Medicinal Chemistry Anticancer Drug Combinations, How Far We can Go Through?
Anti-Cancer Agents in Medicinal Chemistry The Glutathione System and its Regulation by Neurohormone Melatonin in the Central Nervous System
Central Nervous System Agents in Medicinal Chemistry CETUXIMAB: From Bench to Bedside
Current Cancer Drug Targets Angiotensin II Receptor Blocker as an Inverse Agonist: A Current Perspective
Current Hypertension Reviews Nanoemulsion Encapsulation and In Vitro SLN Models of Delivery for Cytotoxic Methotrexate
Current Drug Discovery Technologies Imaging Virus-Associated Cancer
Current Pharmaceutical Design Bortezomib in the Treatment of Cancer
Recent Patents on Anti-Cancer Drug Discovery Development of Taxol and Other Endophyte Produced Anti-Cancer Agents
Recent Patents on Anti-Cancer Drug Discovery