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
-
Therapeutic Potential of Perineural Invasion, Hypoxia and Desmoplasia in Pancreatic Cancer
Current Pharmaceutical Design An Overview of Labeled Porphyrin Molecules in Medical Imaging
Recent Patents and Topics on Imaging (Discontinued) Polyethyleneimine-Based Nanocarriers for Gene Delivery
Current Pharmaceutical Design HIF-1 Signaling in Drug Resistance to Chemotherapy
Current Medicinal Chemistry Lipidomic Analysis of Glioblastoma Multiforme Using Mass Spectrometry
Current Metabolomics Nasal Polyposis: An Overview of Differential Diagnosis and Treatment
Recent Patents on Inflammation & Allergy Drug Discovery Biosafety of Herpesvirus Vectors
Current Gene Therapy Drug Design Targeting the CXCR4/CXCR7/CXCL12 Pathway
Current Topics in Medicinal Chemistry The Effectiveness of Nanoparticles on Gene Therapy for Glioblastoma Cells Apoptosis: A Systematic Review
Current Gene Therapy Colloidal Supramolecular Aggregates for Therapeutic Application in Neuromedicine
Current Medicinal Chemistry Heparin Affin Regulatory Peptide: A New Target for Tumour Therapy?
Current Cancer Drug Targets Fighting Fire with Fire: A Patent for the Combined Application of Oncolytic Herpes Viruses and Antiangiogenic Agents in the Battle Against Human Cancers
Recent Patents on Anti-Cancer Drug Discovery β-Lactams as Neuroprotective Agents
Anti-Infective Agents in Medicinal Chemistry The Endothelin Axis as Therapeutic Target in Human Malignancies: Present and Future
Current Pharmaceutical Design Synthesis of (R)-2-benzylmorpholine employing catalytic stereospecific rearrangement of L-Phenylalaninol
Letters in Organic Chemistry Mechano-Regulation of Alternative Splicing
Current Genomics Conditionally Replicating Adenoviruses for Cancer Treatment
Current Cancer Drug Targets Potential Therapeutic Application of Chondroitin Sulfate/Dermatan Sulfate
Current Drug Discovery Technologies Recent Evidence of the Regulatory Role of PPARs in Neural Stem Cells and Their Underlying Mechanisms for Neuroprotective Effects
Current Stem Cell Research & Therapy The Spleen Tyrosine Kinase (Syk) in Human Disease, Implications for Design of Tyrosine Kinase Inhibitor Based Therapy
Current Pharmaceutical Design