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
-
Editorial [Hot Topic: Novel Peptide-Based Scaffolds for Drug Discovery (Executive Guest Editor: Julio A. Camarero)]
Current Pharmaceutical Design The Impacts of Non-coding RNAs and N<sup>6</sup>-Methyladenosine on Cancer: Past, Present and Future
Current Cancer Drug Targets Stem Cells in Brain Tumorigenesis and their Impact on Therapy
Current Stem Cell Research & Therapy Nanoparticle Coated Viral Vectors for Gene Therapy
Current Biotechnology Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia
Anti-Cancer Agents in Medicinal Chemistry Remyelination in Multiple Sclerosis: The Therapeutic Potential of Neural and Mesenchymal Stem/Progenitor Cells
Current Signal Transduction Therapy An Integrative Systems Analysis of High-grade Glioma Cell Lines: TLRs, Wnt, BRCA1, Netrins, STXBP1 and MDH1 Provide Putative Molecular Targets for Therapeutic Intervention
Current Pharmacogenomics and Personalized Medicine Boron Nitride Nanotubes: Production, Properties, Biological Interactions and Potential Applications as Therapeutic Agents in Brain Diseases
Current Nanoscience Targeting Cancer Stem Cells: Promises and Challenges
Anti-Cancer Agents in Medicinal Chemistry EDITORIAL (Hot Topic: Cancer Chemoresistance and DNA Repair)
Current Medicinal Chemistry Targeting Indoleamine 2,3-dioxygenase (IDO) to Counteract Tumour- Induced ImmuneDysfunction: From Biochemistry to Clinical Development
Endocrine, Metabolic & Immune Disorders - Drug Targets Small Molecule Inhibitors Targeting Key Proteins in the DNA Damage Response for Cancer Therapy
Current Medicinal Chemistry Synthesis and Evaluation of <sup>198</sup>Au/PAMAM-MPEG-FA against Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry The Epidermal Growth Factor Receptor as a Therapeutic Target in Glioblastoma Multiforme and other Malignant Neoplasms
Anti-Cancer Agents in Medicinal Chemistry Current Development of Metal Complexes with Diamine Ligands as Potential Anticancer Agents
Current Medicinal Chemistry Marine Natural Products as a Promising Source of Therapeutic Compounds to Target Cancer Stem Cells
Current Medicinal Chemistry CASC15: A Tumor-Associated Long Non-Coding RNA
Current Pharmaceutical Design Biochemical Markers of Autoimmune Diseases of the Nervous System
Current Pharmaceutical Design Mass Spectrometric Imaging of the Nervous System
Current Pharmaceutical Design A New Approach for Cancer Immunotherapy Based on the Cancer Stem Cell Antigens Properties
Current Molecular Medicine