Abstract
Brain tumors, primary and metastatic, are a cause of significant mortality and morbidity. Radiotherapy (RT) forms an integral part of the treatment of brain tumors. Intrinsic relative tumor radio-resistance, normal tissue tolerance and impact on neurocognitive function, all limit the efficacy of RT. Radiosensitizers can potentially increase efficacy on tumors while maintaining normal tissue toxicity, with or without inherent cytotoxicity. This article reviews the evolution of evidence with use of non-cytotoxic radiosensitizers in brain radiotherapy and their status at the end of the first decade of this millennium. Considering, the era of development and mechanism of action, these agents are classified as first, second and third-generation non-cytotoxic radiosensitizers. The last millennium involved elaboration of first-generation compounds including halogenated pyrimidines, hypoxic cell sensitizers (e.g. imidazoles) and glycolytic inhibitors (e.g. lonidamine). The first decade of this millennium has highlighted redox modulators like motexafin gadolinium and newer hypoxic cell sensitizers like efaproxiral, which have shown promise. However, phase III trials and meta-analyses have not identified a clear winner though the second-generation has shown some rays of hope. Recent research has focused on expanding the horizon by studying modulation of newer molecular pathways like DNA repair, microtubule stabilization, cytokine function and nuclear factor-kappa beta (NF-KB) in order to increase RT efficacy. The review concludes by summarizing the class of evidence and the level of recommendation available for use of non-cytotoxic radiosensitizers in brain RT.
Keywords: Astrocytoma, brain, glioma, glioblastoma, metastasis, radiosensitizers, radiotherapy, (18)Fluoromisonidazole, Karnofsky Performance Scale, Motexafin Gadolinium, High-grade gliomas, Difluromethylornithine, Cyclo-Oxygenase-2, Phosphatase and tensin homolog deleted on chromosome 10, Trans Sodium Crocetinate, Procarbazine, lomustine and vincristine
Current Cancer Drug Targets
Title: Non-Cytotoxic Radiosensitizers in Brain Radiotherapy: Journey Till the First Decade of this Millennium
Volume: 12 Issue: 3
Author(s): P. Mohindra, R. N. Sinha, R. J. Andrews and D. Khuntia
Affiliation:
Keywords: Astrocytoma, brain, glioma, glioblastoma, metastasis, radiosensitizers, radiotherapy, (18)Fluoromisonidazole, Karnofsky Performance Scale, Motexafin Gadolinium, High-grade gliomas, Difluromethylornithine, Cyclo-Oxygenase-2, Phosphatase and tensin homolog deleted on chromosome 10, Trans Sodium Crocetinate, Procarbazine, lomustine and vincristine
Abstract: Brain tumors, primary and metastatic, are a cause of significant mortality and morbidity. Radiotherapy (RT) forms an integral part of the treatment of brain tumors. Intrinsic relative tumor radio-resistance, normal tissue tolerance and impact on neurocognitive function, all limit the efficacy of RT. Radiosensitizers can potentially increase efficacy on tumors while maintaining normal tissue toxicity, with or without inherent cytotoxicity. This article reviews the evolution of evidence with use of non-cytotoxic radiosensitizers in brain radiotherapy and their status at the end of the first decade of this millennium. Considering, the era of development and mechanism of action, these agents are classified as first, second and third-generation non-cytotoxic radiosensitizers. The last millennium involved elaboration of first-generation compounds including halogenated pyrimidines, hypoxic cell sensitizers (e.g. imidazoles) and glycolytic inhibitors (e.g. lonidamine). The first decade of this millennium has highlighted redox modulators like motexafin gadolinium and newer hypoxic cell sensitizers like efaproxiral, which have shown promise. However, phase III trials and meta-analyses have not identified a clear winner though the second-generation has shown some rays of hope. Recent research has focused on expanding the horizon by studying modulation of newer molecular pathways like DNA repair, microtubule stabilization, cytokine function and nuclear factor-kappa beta (NF-KB) in order to increase RT efficacy. The review concludes by summarizing the class of evidence and the level of recommendation available for use of non-cytotoxic radiosensitizers in brain RT.
Export Options
About this article
Cite this article as:
Mohindra P., N. Sinha R., J. Andrews R. and Khuntia D., Non-Cytotoxic Radiosensitizers in Brain Radiotherapy: Journey Till the First Decade of this Millennium, Current Cancer Drug Targets 2012; 12 (3) . https://dx.doi.org/10.2174/156800912799277494
DOI https://dx.doi.org/10.2174/156800912799277494 |
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
-
Recent Advances and Strategies in Tumor Vasculature Targeted Nano-Drug Delivery Systems
Current Pharmaceutical Design Iron Oxide Nanoparticle Platform for Biomedical Applications
Current Medicinal Chemistry Targeting Cell Death in Tumors by Activating Caspases
Current Cancer Drug Targets Farnesylated Proteins as Anticancer Drug Targets: From Laboratory to the Clinic
Current Medicinal Chemistry - Anti-Cancer Agents Editorial [Hot Topic: Emerging Treatment Strategies for Malignant Gliomas]
Current Drug Discovery Technologies Antibody Engineering, Virus Retargeting and Cellular Immunotherapy: One Ring to Rule Them All?
Current Gene Therapy Beyond Oncolytic Virotherapy: Replication-Competent Retrovirus Vectors for Selective and Stable Transduction of Tumors
Current Gene Therapy Characteristics of Brain Tumor Stem Cells and the Rationale for Applying Tyrosine Kinase Inhibitors as Potential Targeting Agents
Recent Patents on Regenerative Medicine Withdrawal Notice: The Recent Advancement in the Field of Super Paramagnetic Iron Oxide Nanoparticles (SPIONs) for Aiming Breast Cancer
Current Drug Metabolism Anticancer Mechanisms of Berberine: A Good Choice for Glioblastoma Multiforme Therapy
Current Medicinal Chemistry Tumor Stroma Manipulation By MSC
Current Drug Targets Application of Spray-drying and Electrospraying/Electospinning for Poorly Watersoluble Drugs: A Particle Engineering Approach
Current Pharmaceutical Design Restoring TRAIL Induced Apoptosis Using Naturopathy. Hercules Joins Hand with Nature to Triumph Over Lernaean Hydra
Current Genomics Regulatable Gene Expression Systems for Gene Therapy
Current Gene Therapy Tyrosine Kinase Inhibitors
Current Cancer Drug Targets Targeted Enzyme Prodrug Therapies
Mini-Reviews in Medicinal Chemistry Potential Gene Therapy Strategies for Cancer Stem Cells
Current Gene Therapy Peptide Therapeutics in Neurodegenerative Disorders
Current Medicinal Chemistry OX40:OX40L Axis: Emerging Targets for Immunotherapy of Human Disease
Current Immunology Reviews (Discontinued) Brain Perfusion In Sepsis
Current Vascular Pharmacology