Abstract
Chemotherapy-induced neurotoxicity is a significant complication in the successful treatment of many cancers. Neurotoxicity may develop as a consequence of treatment with platinum analogues (cisplatin, oxaliplatin, carboplatin), taxanes (paclitaxel, docetaxel), vinca alkaloids (vincristine) and more recently, thalidomide and bortezomib. Typically, the clinical presentation reflects an axonal peripheral neuropathy with glove-and-stocking distribution sensory loss, combined with features suggestive of nerve hyperexcitability including paresthesia, dysesthesia, and pain. These symptoms may be disabling, adversely affecting activities of daily living and thereby quality of life. The incidence of chemotherapy-induced neurotoxicity appears critically related to cumulative dose and infusion duration, while individual risk factors may also influence the development and severity of neurotoxicity. Differences in structural properties between chemotherapies further contribute to variations in clinical presentation. The mechanisms underlying chemotherapy-induced neurotoxicity are diverse and include damage to neuronal cell bodies in the dorsal root ganglion and axonal toxicity via transport deficits or energy failure. More recently, axonal membrane ion channel dysfunction has been identified, including studies in patients treated with oxaliplatin which have revealed alterations in axonal Na+ channels, suggesting that prophylactic pharmacological therapies aimed at modulating ion channel activity may prove useful in reducing neurotoxicity. As such, improved understanding of the pathophysiology of chemotherapy-induced neurotoxicity will inevitably assist in the development of future neuroprotective strategies and in the design of novel chemotherapies with improved toxicity profiles.
Keywords: Chemotherapy, platinum, oxaliplatin, taxane, neurotoxicity, neuropathy, neuroprotection
Current Medicinal Chemistry
Title: Mechanisms Underlying Chemotherapy-Induced Neurotoxicity and the Potential for Neuroprotective Strategies
Volume: 15 Issue: 29
Author(s): S. B. Park, A. V. Krishnan, C. S-Y. Lin, D. Goldstein, M. Friedlander and M. C. Kiernan
Affiliation:
Keywords: Chemotherapy, platinum, oxaliplatin, taxane, neurotoxicity, neuropathy, neuroprotection
Abstract: Chemotherapy-induced neurotoxicity is a significant complication in the successful treatment of many cancers. Neurotoxicity may develop as a consequence of treatment with platinum analogues (cisplatin, oxaliplatin, carboplatin), taxanes (paclitaxel, docetaxel), vinca alkaloids (vincristine) and more recently, thalidomide and bortezomib. Typically, the clinical presentation reflects an axonal peripheral neuropathy with glove-and-stocking distribution sensory loss, combined with features suggestive of nerve hyperexcitability including paresthesia, dysesthesia, and pain. These symptoms may be disabling, adversely affecting activities of daily living and thereby quality of life. The incidence of chemotherapy-induced neurotoxicity appears critically related to cumulative dose and infusion duration, while individual risk factors may also influence the development and severity of neurotoxicity. Differences in structural properties between chemotherapies further contribute to variations in clinical presentation. The mechanisms underlying chemotherapy-induced neurotoxicity are diverse and include damage to neuronal cell bodies in the dorsal root ganglion and axonal toxicity via transport deficits or energy failure. More recently, axonal membrane ion channel dysfunction has been identified, including studies in patients treated with oxaliplatin which have revealed alterations in axonal Na+ channels, suggesting that prophylactic pharmacological therapies aimed at modulating ion channel activity may prove useful in reducing neurotoxicity. As such, improved understanding of the pathophysiology of chemotherapy-induced neurotoxicity will inevitably assist in the development of future neuroprotective strategies and in the design of novel chemotherapies with improved toxicity profiles.
Export Options
About this article
Cite this article as:
Park B. S., Krishnan V. A., Lin S-Y. C., Goldstein D., Friedlander M. and Kiernan C. M., Mechanisms Underlying Chemotherapy-Induced Neurotoxicity and the Potential for Neuroprotective Strategies, Current Medicinal Chemistry 2008; 15 (29) . https://dx.doi.org/10.2174/092986708786848569
DOI https://dx.doi.org/10.2174/092986708786848569 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
The Role of Dietary Polyphenols in the Management of Inflammatory Bowel Disease
Current Pharmaceutical Biotechnology Meet Our Editorial Board Member:
Current Medicinal Chemistry Antihistamine Use in Dermatologic Disorders
Current Medicinal Chemistry - Anti-Inflammatory & Anti-Allergy Agents Sphingolipid Modulation: A Strategy for Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Somatostatin: A Hormone for the Heart?
Current Vascular Pharmacology Phenothiazine Derivatives as Potential Antiproliferative Agents: A Mini- Review
Mini-Reviews in Organic Chemistry Diarylurea: A Privileged Scaffold in Drug Discovery and Therapeutic Development
Current Medicinal Chemistry Base Excision Repair: Contribution to Tumorigenesis and Target in Anticancer Treatment Paradigms
Current Medicinal Chemistry Calpain-Associated Proteolytic Regulation of the Stromal Microenvironment in Cancer
Current Pharmaceutical Design Editorial
Current Medical Imaging Is Fast Food Addictive?
Current Drug Abuse Reviews Targeted Drug Delivery to Cancer Stem Cells through Nanotechnological Approaches
Current Stem Cell Research & Therapy Melittin: A Natural Peptide with Expanded Therapeutic Applications
The Natural Products Journal TGF-Beta: a Master Switch in Tumor Immunity
Current Pharmaceutical Design Targeted Nanoparticles for Co-delivery of 5-FU and Nitroxoline, a Cathepsin B Inhibitor, in HepG2 Cells of Hepatocellular Carcinoma
Anti-Cancer Agents in Medicinal Chemistry Retinol-Binding Protein 4 and New Adipocytokines in Nonalcoholic Fatty Liver Disease
Current Pharmaceutical Design Perspectives of Protein Kinase C (PKC) Inhibitors as Anti-Cancer Agents
Mini-Reviews in Medicinal Chemistry Solid Lipid Nanoparticles and Chitosan-coated Solid Lipid Nanoparticles as Promising Tool for Silybin Delivery: Formulation, Characterization, and In vitro Evaluation
Current Drug Delivery Targeted Therapy of Ovarian Cancer with Angiogenesis Inhibitors
Current Drug Targets Domperidone in Parkinson’s Disease: A Perilous Arrhythmogenic or the Gold Standard?
Current Drug Safety