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Published on: October 27, 2014
Perspectives in the treatment of malignant gliomas in adults
N Andratschke1, A L Grosu, M Molls
1Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston 77025, USA.
Abstract:
Over the last two decades, after establishing the role of postoperative radiotherapy for malignant gliomas, no definitive improvement in survival rate could be observed, despite advances in established treatment modalities such as radiotherapy and chemotherapy. Progress in exploration of the biology of these tumours allowed for translational research projects and the development of rational new approaches, such as gene therapy and immunotherapy, that could interfere with established treatment regimens or be used independently. Possible strategies include the restoration of defective cancer-inhibitory genes, cell transduction or transfection with antisense DNA corresponding to genes coding for growth factors and their receptors, or with the so-called 'suicide genes'. Several antiangiogenic approaches such as administration of thalidomide, protamine, or monoclonal antibodies against vascular endothelial growth factor have been developed, too. Further treatment possibilities include modulation of drug resistance, e.g. by P-glycoprotein antagonists or 06-alkyl-guanine-DNA-transferase inhibitors, inhibition of matrix metalloproteinases, inhibition of protein kinase C and administration of agents such as phenylbutyrate or valproic acid that showed promising antiproliferative effects in vitro. This review discusses the available laboratory and clinical data as well as recent advances in our knowledge about prognostic and predictive factors and their implications for the design of future clinical trials.
Insights
Despite advances in radiotherapy and chemotherapy for malignant gliomas, survival rates remain stagnant. Novel strategies like gene therapy, immunotherapy, and antiangiogenic approaches offer new hope for improved treatment outcomes in brain tumors.
Area of Science:
- Neuro-oncology
- Translational Cancer Research
- Molecular Biology
Background:
- Malignant gliomas have shown limited survival improvements with conventional radiotherapy and chemotherapy over the past two decades.
- Advances in understanding tumor biology have paved the way for novel therapeutic strategies.
Purpose of the Study:
- To review current laboratory and clinical data on emerging treatments for malignant gliomas.
- To discuss the implications of prognostic and predictive factors for future clinical trial design.
Main Methods:
- Review of existing literature on gene therapy, immunotherapy, and antiangiogenic approaches.
- Analysis of data on modulating drug resistance and inhibiting specific molecular targets.
- Discussion of novel agents with antiproliferative effects.
Main Results:
- Gene therapy strategies include restoring tumor-suppressor genes, using antisense DNA, and employing 'suicide genes'.
- Antiangiogenic therapies and methods to overcome drug resistance (e.g., targeting P-glycoprotein, O6-alkyl-guanine-DNA-transferase) are under investigation.
- Agents like phenylbutyrate and valproic acid demonstrate promising in vitro antiproliferative activity.
Conclusions:
- New therapeutic avenues beyond traditional treatments are crucial for improving malignant glioma outcomes.
- Understanding prognostic and predictive factors is essential for developing effective future clinical trials.
- Targeted therapies, including gene therapy and immunotherapy, hold potential for advancing brain tumor treatment.
