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Primary Orthotopic Glioma Xenografts Recapitulate Infiltrative Growth and Isocitrate Dehydrogenase I Mutation
Published on: January 14, 2014
Changing paradigms for targeted therapies against diffuse infiltrative gliomas: tackling a moving target
Candice D Carpenter1, Iyad Alnahhas2, Javier Gonzalez1,2
1a Department of Neurosurgery , The Ohio State University Wexner Medical Center , Columbus , OH , USA.
Abstract:
Introduction: Gliomas are highly heterogeneous primary brain tumors which result in a disproportionately high degree of morbidity and mortality despite their locoregional occurrence. Advances in the understanding of the biological makeup of these malignancies have yielded a number of potential tumor-driving pathways which have been identified as rational targets for therapy. However, early trials of agents that target these pathways have uniformly failed to yield improvement in outcomes in patients with malignant gliomas. Areas covered: This review provides an overview of the most common biological features of gliomas and the strategies to target the same; in addition, the current status of immunotherapy and biological therapies are outlined and the future directions to tackle the challenges of therapy for gliomas are examined. Expert opinion: The limitations of current treatments are attributed to the inability of most of these agents to cross the blood-brain barrier and to the intrinsic heterogeneity of the tumors that result in treatment resistance. The recent emergence of immune-mediated and biological therapies and of agents that target metabolic pathways in gliomas have provided strategies that may overcome tumor heterogeneity and ongoing trials of such agents are anticipated to yield improved outcomes.
Insights
New glioma therapies targeting tumor heterogeneity and metabolism show promise. Despite challenges like the blood-brain barrier, emerging immunotherapies and biological agents offer hope for improved patient outcomes in malignant gliomas.
Area of Science:
- Neuro-oncology
- Cancer Biology
- Translational Medicine
Background:
- Gliomas are aggressive primary brain tumors with high morbidity and mortality.
- Despite identified therapeutic targets, early treatments for malignant gliomas have shown limited success.
- Tumor heterogeneity and the blood-brain barrier are significant challenges in glioma treatment.
Purpose of the Study:
- To review common biological features of gliomas and therapeutic strategies.
- To outline the current status of immunotherapy and biological therapies for gliomas.
- To examine future directions for overcoming challenges in glioma treatment.
Main Methods:
- Literature review of glioma biology and therapeutic targets.
- Analysis of current immunotherapy and biological therapy approaches.
- Examination of emerging strategies targeting tumor heterogeneity and metabolism.
Main Results:
- Established targeted therapies have faced limitations due to the blood-brain barrier and tumor heterogeneity.
- Novel approaches including immunotherapy and metabolic pathway targeting are under investigation.
- Ongoing clinical trials are exploring these advanced therapeutic strategies.
Conclusions:
- Overcoming tumor heterogeneity and improving drug delivery are critical for effective glioma treatment.
- Emerging immune-mediated and biological therapies hold potential to improve outcomes.
- Future research and clinical trials are essential to advance glioma therapy.
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