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Updated: Aug 11, 2026
Combination Radiotherapy in an Orthotopic Mouse Brain Tumor Model
Published on: March 6, 2012
Biology and treatment of malignant glioma
1Division of Neurology, Barrow Neurological Institute, Phoenix, Arizona, USA.
Abstract:
A large number of oncogenes have been identified as aberrant in gliomas, but only the erbB oncogene (gene encoding the epidermal growth factor receptor [EGFR]) is amplified in an appreciable number. The loss or mutation of tumor-suppressor genes located on different autosomes may be associated with progression of malignant gliomas. The p53 tumor-suppressor gene (located on chromosome 17) is frequently associated with the loss of one allele in malignant gliomas, although a large number of malignant gliomas have no p53 mutations. Some of the latter tumors have an amplified murine double minute 2 (MDM2) gene, which suppresses p53 gene activity. Genetic material from chromosome 10 may also be lost, especially in glioblastoma multiforme. In addition to the aberrant expression of EGFR, another growth factor, platelet-derived growth factor, or PDGF (ligand and/or receptors) can be overexpressed, giving cells a selective growth advantage. The blood-brain barrier is substantially altered in malignant gliomas, resulting in cerebral edema. Therapy for malignant gliomas includes surgery, radiation therapy, and chemotherapy. Surgical resection that leaves little residual tumor produces longer survival than less vigorous surgery. Radiation therapy to a dose of at least 60 Gy is required to treat malignant gliomas. Increased survival beyond that produced by standard external radiotherapy requires much larger doses; interstitial radiotherapy permits such dosing. Radiosurgery is being tested. Chemotherapy with nitrosoureas is modestly useful but appears to benefit patients with anaplastic astrocytoma more so than those with glioblastoma.
Insights
Malignant gliomas involve oncogene amplification like EGFR and tumor suppressor gene alterations. Treatment includes surgery, radiation therapy, and chemotherapy, with maximal tumor resection and high-dose radiation improving survival.
Area of Science:
- Neuro-oncology
- Cancer Genetics
- Clinical Oncology
Background:
- Malignant gliomas exhibit numerous oncogene aberrations, notably epidermal growth factor receptor (EGFR) amplification.
- Tumor suppressor gene alterations, including p53 mutations or loss of heterozygosity, and MDM2 amplification are implicated in glioma progression.
- Loss of genetic material from chromosome 10 is observed, particularly in glioblastoma multiforme.
- Overexpression of growth factors like platelet-derived growth factor (PDGF) provides a proliferative advantage.
Purpose of the Study:
- To review the genetic alterations, growth factor involvement, and therapeutic strategies for malignant gliomas.
- To highlight the role of specific oncogenes and tumor suppressor genes in glioma development and progression.
- To discuss the impact of current treatment modalities on patient survival.
Main Methods:
- Review of genetic alterations in malignant gliomas, including oncogene amplification and tumor suppressor gene mutations.
- Analysis of growth factor signaling pathways implicated in glioma proliferation.
- Evaluation of therapeutic approaches such as surgery, radiation therapy, and chemotherapy.
Main Results:
- Epidermal growth factor receptor (EGFR) is the most frequently amplified oncogene in gliomas.
- p53 tumor suppressor gene alterations and MDM2 amplification are common, alongside chromosome 10 deletions.
- Enhanced growth factor signaling (EGFR, PDGF) contributes to tumor growth.
- Maximal surgical resection and high-dose radiation therapy (≥60 Gy) improve survival outcomes.
- Chemotherapy, particularly nitrosoureas, offers modest benefits, with greater efficacy in anaplastic astrocytoma.
Conclusions:
- Malignant gliomas are characterized by a complex interplay of genetic alterations and growth factor dysregulation.
- Optimized surgical and radiation strategies are crucial for improving patient survival.
- Further research into targeted therapies and combination treatments is warranted.
