Abstract
Background: Glioblastoma multiforme (GBM) is the most malignant histological type of glioma. It exhibits an extremely aggressive action including invasion of large zones of brain parenchyma. Even after the application of surgery, radio and chemotherapy, the effect and survival for patients with GBM continue to be very poor. The PI3K/AKT/mTOR is a key pathway in the regulation of the proliferation of cancer cells. This is the reason to consider the mTOR inhibitors such as rapamycin analogs as an encouraging therapy for malignant glioma, but current investigations suggest that single inhibition of mTOR may be insufficient. For this reason, there is a need for the use of more than one agent rationally combined.
Methods: In this study, we have evaluated the therapeutic potential of the combination of two different drugs: intraperitoneal rapamycin and convection enhanced delivery of nanoliposomes containing the topoisomerase I inhibitor CPT-11. The effect was analyzed by flow cytometry, cell growth, immunocytochemistry and immunohistochemistry, and rodent orthotopic xenograft survival analysis.
Results: The combination presented remarkable efficacy in a survival study. We present an increase in survival of 6-fold in xenotransplanted animals without rise in toxicity.
Conclusion: In summary, we propose a very powerful new combination therapy for glioma.
Keywords: Combination, CPT-11, glioma, rapamycin, therapy.
Current Cancer Drug Targets
Title:Combination Therapy of Intraperitoneal Rapamycin and Convection- Enhanced Delivery of Nanoliposomal CPT-11 in Rodent Orthotopic Brain Tumor Xenografts
Volume: 15 Issue: 4
Author(s): Marina Mendiburu-Elicabe and Jon Gil-Ranedo
Affiliation:
Keywords: Combination, CPT-11, glioma, rapamycin, therapy.
Abstract: Background: Glioblastoma multiforme (GBM) is the most malignant histological type of glioma. It exhibits an extremely aggressive action including invasion of large zones of brain parenchyma. Even after the application of surgery, radio and chemotherapy, the effect and survival for patients with GBM continue to be very poor. The PI3K/AKT/mTOR is a key pathway in the regulation of the proliferation of cancer cells. This is the reason to consider the mTOR inhibitors such as rapamycin analogs as an encouraging therapy for malignant glioma, but current investigations suggest that single inhibition of mTOR may be insufficient. For this reason, there is a need for the use of more than one agent rationally combined.
Methods: In this study, we have evaluated the therapeutic potential of the combination of two different drugs: intraperitoneal rapamycin and convection enhanced delivery of nanoliposomes containing the topoisomerase I inhibitor CPT-11. The effect was analyzed by flow cytometry, cell growth, immunocytochemistry and immunohistochemistry, and rodent orthotopic xenograft survival analysis.
Results: The combination presented remarkable efficacy in a survival study. We present an increase in survival of 6-fold in xenotransplanted animals without rise in toxicity.
Conclusion: In summary, we propose a very powerful new combination therapy for glioma.
Export Options
About this article
Cite this article as:
Mendiburu-Elicabe Marina and Gil-Ranedo Jon, Combination Therapy of Intraperitoneal Rapamycin and Convection- Enhanced Delivery of Nanoliposomal CPT-11 in Rodent Orthotopic Brain Tumor Xenografts, Current Cancer Drug Targets 2015; 15 (4) . https://dx.doi.org/10.2174/1568009615666150225123120
DOI https://dx.doi.org/10.2174/1568009615666150225123120 |
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
-
Laminin-332-Integrin Interaction: A Target For Cancer Therapy?
Current Medicinal Chemistry Translational Optical Imaging in Diagnosis and Treatment of Cancer
Current Pharmaceutical Biotechnology Microtubule Targeting Agents: A Benchmark in Cancer Therapy
Current Drug Therapy Ribozymes, DNAzymes and Small Interfering RNAs as Therapeutics
Current Drug Targets Kinin Receptors in Vascular Biology and Pathology
Current Vascular Pharmacology CD147/EMMPRIN and CD44 are Potential Therapeutic Targets for Metastatic Prostate Cancer
Current Cancer Drug Targets Conditionally Replicating Adenoviruses for Cancer Treatment
Current Cancer Drug Targets Recent Advances in Experimental Molecular Therapeutics for Malignant Gliomas
Current Medicinal Chemistry - Anti-Cancer Agents ADAM19/Adamalysin 19 Structure, Function, and Role as a Putative Target in Tumors and Inflammatory Diseases
Current Pharmaceutical Design Antioxidant Supplementation on Cancer Risk and During Cancer Therapy: An Update
Current Topics in Medicinal Chemistry Non-Coding RNA in Brain Development and Disorder
Current Medicinal Chemistry Colostral Proline-Rich Polypeptides - Immunoregulatory Properties and Prospects of Therapeutic Use in Alzheimers Disease
Current Alzheimer Research Targeting the Atypical Chemokine Receptor ACKR3/CXCR7: Phase 1 - Phage Display Peptide Identification and Characterization
Current Topics in Medicinal Chemistry The Macrophage Stimulating Protein/Ron Pathway as a Potential Therapeutic Target to Impede Multiple Mechanisms Involved in Breast Cancer Progression
Current Drug Targets Porphyrin-based Sensitizers in the Detection and Treatment of Cancer: Recent Progress
Current Medicinal Chemistry - Anti-Cancer Agents Emerging Concepts in the Analysis of Mitochondrial Genome Instability
Current Genomics Gene Selection in Multi-class Imbalanced Microarray Datasets Using Dynamic Length Particle Swarm Optimization
Current Bioinformatics Medicinal Compound Celastrol As a Potential Clinical Anticancer Drug: Lessons Learned From Preclinical Studies
Clinical Cancer Drugs The Role of PET/CT and SPECT/CT in Oncology Drug Development
Current Molecular Imaging (Discontinued) An Automatic Glioma Segmentation System Using a Multilevel Attention Pyramid Scene Parsing Network
Current Medical Imaging