Abstract
The median survival of patients with glioblastoma treated by surgery, radiotherapy and chemotherapy is in the range of 12 months. These limits in the efficacy of current treatment modalities call for the development of novel therapeutic approaches targeting the specific biological features of this type of cancer. Glioblastomas are a rich source of immunosuppressive molecules which may interfere with immune recognition and rejection as well as clinical strategies of active immunotherapy. The most prominent glioblastoma-associated immunosuppressant is the cytokine, transforming growth factor (TGF)β, a multifunctional cytokine which not only interferes with multiple steps of afferent and efferent immune responses, but also stimulates migration, invasion and angiogenesis. The complex regulation of TGFβ bioavailability includes its synthesis as a proprotein, proteolytic processing by furin-like proteases, assembly in a latent complex, and finally liberation from latency by multiple effector mechanisms, a process collectively referred to as activation. Several in vitro paradigms and rodent glioma models have been used to demonstrate that the antagonism of TGFβ holds promise for the treatment of glioblastoma, employing antisense strategies, inhibition of pro-TGFβ processing, scavenging TGFβ by decorin, or blocking TGFβ activity by specific TGFβ receptor (TGFβR) I kinase antagonists. Moreover, the local application of TGFβ2 antisense oligonucleotides is currently evaluated in a randomized clinical trial for recurrent malignant glioma. In summary, we propose that TGF- β-antagonistic treatment strategies are among the most promising of the current innovative approaches for glioblastoma, particularly in conjunction with novel approaches of cellular immunotherapy and vaccination.
Keywords: Astrocytoma, apoptosis, brain, glioma, immunosuppression, immunotherapy, TGFβ
Current Pharmaceutical Design
Title: Transforming Growth Factor-β: A Molecular Target for the Future Therapy of Glioblastoma
Volume: 12 Issue: 3
Author(s): Wolfgang Wick, Ulrike Naumann and Michael Weller
Affiliation:
Keywords: Astrocytoma, apoptosis, brain, glioma, immunosuppression, immunotherapy, TGFβ
Abstract: The median survival of patients with glioblastoma treated by surgery, radiotherapy and chemotherapy is in the range of 12 months. These limits in the efficacy of current treatment modalities call for the development of novel therapeutic approaches targeting the specific biological features of this type of cancer. Glioblastomas are a rich source of immunosuppressive molecules which may interfere with immune recognition and rejection as well as clinical strategies of active immunotherapy. The most prominent glioblastoma-associated immunosuppressant is the cytokine, transforming growth factor (TGF)β, a multifunctional cytokine which not only interferes with multiple steps of afferent and efferent immune responses, but also stimulates migration, invasion and angiogenesis. The complex regulation of TGFβ bioavailability includes its synthesis as a proprotein, proteolytic processing by furin-like proteases, assembly in a latent complex, and finally liberation from latency by multiple effector mechanisms, a process collectively referred to as activation. Several in vitro paradigms and rodent glioma models have been used to demonstrate that the antagonism of TGFβ holds promise for the treatment of glioblastoma, employing antisense strategies, inhibition of pro-TGFβ processing, scavenging TGFβ by decorin, or blocking TGFβ activity by specific TGFβ receptor (TGFβR) I kinase antagonists. Moreover, the local application of TGFβ2 antisense oligonucleotides is currently evaluated in a randomized clinical trial for recurrent malignant glioma. In summary, we propose that TGF- β-antagonistic treatment strategies are among the most promising of the current innovative approaches for glioblastoma, particularly in conjunction with novel approaches of cellular immunotherapy and vaccination.
Export Options
About this article
Cite this article as:
Wick Wolfgang, Naumann Ulrike and Weller Michael, Transforming Growth Factor-β: A Molecular Target for the Future Therapy of Glioblastoma, Current Pharmaceutical Design 2006; 12 (3) . https://dx.doi.org/10.2174/138161206775201901
DOI https://dx.doi.org/10.2174/138161206775201901 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Targeting Cyclooxygenase-2 in Hematological Malignancies: Rationale and Promise
Current Pharmaceutical Design Metabolomic Approach in Probing Drug Candidates
Current Topics in Medicinal Chemistry Antineoplastic Effects of PPARγ Agonists, with a Special Focus on Thyroid Cancer
Current Medicinal Chemistry Cancer Vaccines: Emphasis on Pediatric Cancers
Current Pharmaceutical Design Recent Innovations in Antibody-Mediated, Targeted Particulate Nanotechnology and Implications for Advanced Visualisation and Drug Delivery
Current Nanoscience Reviewing the Role of Resveratrol as a Natural Modulator of Microglial Activities
Current Pharmaceutical Design Bone Regeneration and Repair
Current Stem Cell Research & Therapy Possible Binding Mode Analysis of Pyrazolo-triazole Hybrids as Potential Anticancer Agents through Validated Molecular Docking and 3D-QSAR Modeling Approaches
Letters in Drug Design & Discovery Antiangiogenic Therapy
Current Pharmaceutical Design Can Targeted Therapy be Successful without Metronomic Scheduling ?
Current Topics in Medicinal Chemistry Effect of Prostaglandins on the Regulation of Tumor Growth
Current Medicinal Chemistry - Anti-Cancer Agents Novel Agents Targeting Bioactive Sphingolipids for the Treatment of Cancer
Current Medicinal Chemistry Ion Transporters in Brain Tumors
Current Medicinal Chemistry Key Epigenetic Events Involved in the Maintenance of Breast Cancer Stem Cells
Current Stem Cell Research & Therapy Nanotheranostics in Evidence Based Personalized Medicine
Current Drug Targets FAK and Nanog Cross Talk with p53 in Cancer Stem Cells
Anti-Cancer Agents in Medicinal Chemistry Approaching the Increasing Complexity of Non-small Cell Lung Cancer Taxonomy
Current Pharmaceutical Design The ErbB Receptors and their Ligands in Cancer: An Overview
Current Drug Targets The 9p21 Locus and its Potential Role in Atherosclerosis Susceptibility; Molecular Mechanisms and Clinical Implications
Current Pharmaceutical Design Research Progress on the Mechanisms of Combined Bevacizumab and Radiotherapy
Recent Patents on Anti-Cancer Drug Discovery