Abstract
The mevalonate pathway is important for the generation of isoprene moieties, thereby providing the basis for the biosynthesis of molecules required for maintaining membrane integrity, steroid production and cell respiration. Additionally, isoprene precursors are indispensable for the prenylation of regulatory proteins such as Ras and Ras-homologous (Rho) GTPases. These low molecular weight GTP-binding proteins play key roles in numerous signal transduction pathways stimulated upon activation of cell surface receptors by ligand binding. Thus, Ras/Rho proteins eventually regulate cell proliferation, tumor progression and cell death induced by anticancer therapeutics. Lipid modification of Ras/Rho proteins at their C-terminal CAAX-box is essential for their correct intracellular localization and function. Therefore, pharmacological inhibition of the isoprene metabolism is anticipated to impact the manifold biological functions attributed to Ras/Rho proteins. Here, the pros and cons of compounds that interfere with the mevalonate pathway for cancer treatment are summarized and discussed.
Keywords: Mevalonate pathway, protein prenylation, GTP-binding proteins, metastasis, anticancer drug resistance
Current Cancer Drug Targets
Title: Targeting the Mevalonate Pathway for Improved Anticancer Therapy
Volume: 9 Issue: 5
Author(s): G. Fritz
Affiliation:
Keywords: Mevalonate pathway, protein prenylation, GTP-binding proteins, metastasis, anticancer drug resistance
Abstract: The mevalonate pathway is important for the generation of isoprene moieties, thereby providing the basis for the biosynthesis of molecules required for maintaining membrane integrity, steroid production and cell respiration. Additionally, isoprene precursors are indispensable for the prenylation of regulatory proteins such as Ras and Ras-homologous (Rho) GTPases. These low molecular weight GTP-binding proteins play key roles in numerous signal transduction pathways stimulated upon activation of cell surface receptors by ligand binding. Thus, Ras/Rho proteins eventually regulate cell proliferation, tumor progression and cell death induced by anticancer therapeutics. Lipid modification of Ras/Rho proteins at their C-terminal CAAX-box is essential for their correct intracellular localization and function. Therefore, pharmacological inhibition of the isoprene metabolism is anticipated to impact the manifold biological functions attributed to Ras/Rho proteins. Here, the pros and cons of compounds that interfere with the mevalonate pathway for cancer treatment are summarized and discussed.
Export Options
About this article
Cite this article as:
Fritz G., Targeting the Mevalonate Pathway for Improved Anticancer Therapy, Current Cancer Drug Targets 2009; 9 (5) . https://dx.doi.org/10.2174/156800909789057033
DOI https://dx.doi.org/10.2174/156800909789057033 |
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
Innovative Cancer Drug Targets: A New Horizon in Oncology
Cancer remains one of the most challenging diseases, with its complexity and adaptability necessitating continuous research efforts into more effective and targeted therapeutic approaches. Recent years have witnessed significant progress in understanding the molecular and genetic basis of cancer, leading to the identification of novel drug targets. These include, but ...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
-
Fluorescein-labeled Bacitracin and Daptomycin Conjugates: Synthesis, Fluorescence Imaging and Evaluation
Medicinal Chemistry MDA-7/IL-24-Based Cancer Gene Therapy: Translation from the Laboratory to the Clinic
Current Gene Therapy <sup>90</sup>Y-DOTA-Nimotuzumab: Synthesis of a Promising β− Radiopharmaceutical
Current Radiopharmaceuticals Recent Advances and Developments in Treatment Strategies Against Pancreatic Cancer
Current Clinical Pharmacology Protein Degradation by the Ubiquitin-Proteasome Pathway and Organ Fibrosis
Current Medicinal Chemistry Mesenchymal Stromal Cell Therapy for Cardio Renal Disorders
Current Pharmaceutical Design Roles of TRAF6 in Central Nervous System
Current Neuropharmacology Fluorescence Imaging of Human Cells with a Novel Conjugate of the Antifungal Nystatin
Medicinal Chemistry The Role of IRE1 Signaling in the Central Nervous System Diseases
Current Neuropharmacology Protein Kinases and their Modulation in the Central Nervous System
Current Medicinal Chemistry - Central Nervous System Agents Molecular Mechanisms Regulating the Mitochondrial Targeting of Microsomal Cytochrome P450 EnzymesMolecular Mechanisms Regulating the Mitochondrial Targeting of Microsomal Cytochrome P450 Enzymes
Current Drug Metabolism Current Status and Future Prospects of C1 Domain Ligands as Drug Candidates
Current Topics in Medicinal Chemistry Tumour-Derived Glutamate: Linking Aberrant Cancer Cell Metabolism to Peripheral Sensory Pain Pathways
Current Neuropharmacology Diffuse Intrinsic Pontine Glioma: New Pathophysiological Insights and Emerging Therapeutic Targets
Current Neuropharmacology Salen Mn Complexes Mitigate Radiation Injury in Normal Tissues
Anti-Cancer Agents in Medicinal Chemistry Some Implications of Receptor Kinase Signaling Pathway for Development of Multitargeted Kinase Inhibitors
Current Radiopharmaceuticals Combination of DC Vaccine and Conventional Chemotherapeutics
Anti-Cancer Agents in Medicinal Chemistry Nitric Oxide Synthase Potentiates the Resistance of Cancer Cell Lines to Anticancer Chemotherapeutics
Anti-Cancer Agents in Medicinal Chemistry In Vitro Intestinal Co-Culture Cell Model to Evaluate Intestinal Absorption of Edelfosine Lipid Nanoparticles
Current Topics in Medicinal Chemistry A Nanostructured Silica-Lipid Hybrid to Facilitate Oral SN-38-based Chemotherapy
Drug Delivery Letters