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Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
Published on: January 9, 2019
Incorporating molecular tools into clinical trials and treatment for gliomas?
Andrew B Lassman1, Eric C Holland
1Department of Neurology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA. lassmana@mskcc.org
Purpose Of Review:
Knowledge of the molecular biology of gliomas may improve therapy. This review highlights several recent studies on this topic.
Recent Findings:
Gliomas are the most common primary brain tumors in adults, and remain refractory to therapy despite decades of work. Discoveries in the last several years have led to a better understanding of glioma biology. These include the importance of O6-methylguanine-DNA-methyltransferase (MGMT) in glioblastoma sensitivity to the DNA alkylating chemotherapy temozolomide. In addition, coexpression of phosphatase tensin homolog on chromosome ten (PTEN) and a mutant variant of the epidermal growth factor receptor (EGFRvIII) appears to predict sensitivity of recurrent glioblastomas to EGFR inhibitors. Finally, loss of heterozygosity for chromosomes 1p and 19q correlates with both response to therapy and improved prognosis for patients with oligodendrogliomas. The best way to incorporate these findings into office practice, however, remains unclear, especially in the absence of effective alternatives to currently available treatments. While subdividing gliomas molecularly may allow tailoring of therapy to individual patients based on individual tumor biology, a superior strategy may be to identify common molecular abnormalities that are targets of more universally applicable therapies.
Summary:
It remains unclear how best to integrate recent discoveries regarding glioma molecular biology into clinical practice.
Insights
Recent glioma research reveals key molecular markers like MGMT and EGFRvIII that influence treatment response. Integrating these findings into clinical practice for brain tumors remains a challenge.
Area of Science:
- Neuro-oncology
- Molecular Biology
- Genetics
Background:
- Gliomas are the most common adult primary brain tumors, notoriously difficult to treat.
- Advances in understanding glioma molecular biology offer new therapeutic insights.
- Current treatments for gliomas remain largely ineffective.
Purpose of the Study:
- To review recent molecular biology discoveries in gliomas.
- To highlight how these findings may impact therapy.
Main Methods:
- Review of recent scientific literature on glioma molecular biology.
- Analysis of key molecular markers and their therapeutic implications.
Main Results:
- O6-methylguanine-DNA-methyltransferase (MGMT) status impacts glioblastoma sensitivity to temozolomide.
- Coexpression of PTEN and EGFRvIII predicts glioblastoma response to EGFR inhibitors.
- 1p/19q loss of heterozygosity correlates with improved prognosis in oligodendrogliomas.
Conclusions:
- Integrating new molecular findings into clinical practice for gliomas is not yet clear.
- Tailoring therapy based on individual tumor biology is a potential strategy.
- Identifying common molecular targets for broader therapies may be more effective.
