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Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
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Clinically Actionable Insights into Initial and Matched Recurrent Glioblastomas to Inform Novel Treatment Approaches
H P Ellis1, C E McInerney2, D Schrimpf3
1Brain Tumour Research Centre, University of Bristol, Bristol, UK.
Journal of Oncology
|February 22, 2020
Summary
This study identified actionable mutations in glioblastoma, a common brain tumor with poor survival. Molecular profiling revealed key genetic variations in IDH-wildtype and IDH-mutant tumors, guiding potential new treatments.
Area of Science:
- Neuro-oncology
- Cancer Genomics
- Molecular Pathology
Background:
- Glioblastoma is the most aggressive primary adult brain tumor, with limited survival rates despite current treatments.
- Identifying actionable mutations is critical for developing targeted therapies and improving patient outcomes.
- Recurrent glioblastomas present unique molecular profiles that require detailed investigation.
Purpose of the Study:
- To investigate actionable mutations in matched primary and recurrent glioblastoma tumors.
- To profile glioblastomas using a DNA-based gene panel, examining copy number variations (CNVs) and single nucleotide variants (SNVs).
- To identify potentially pathogenic and clinically actionable variants in both IDH-wildtype (IDHWT) and IDH-mutant (IDHMUT) glioblastomas.
Main Methods:
- Tumor samples from glioblastoma patients were analyzed using a validated DNA-based gene panel.
- Both single nucleotide variants (SNVs) and copy number variations (CNVs) were assessed.
- Public datasets (TCGA and GDC) were utilized to confirm findings and clinical significance.
Main Results:
- Glioblastomas were predominantly IDH-wildtype (n=38) with a smaller cohort of IDH-mutant (n=3).
- Potentially actionable variations were frequently identified in EGFR, PTEN, BRCA1/2, and ATM.
- IDHWT tumors showed impacted pathways including RTK/Ras/PI(3)K, p53, WNT, SHH, NOTCH, Rb, and G-protein, with BRCA1/2 variants in 18% of cases.
- Recurrent tumors, particularly IDHWT, exhibited fewer impacted pathways and specific CNV alterations.
- Variants of unknown significance (VUS) were noted in TSC2, MSH6, TP53, CREBBP, and IDH1, predicted as pathogenic in both subtypes.
Conclusions:
- Detailed molecular profiling is essential for identifying glioblastoma patients eligible for novel therapeutic strategies.
- Actionable mutations, particularly in EGFR, PTEN, BRCA1/2, and ATM, offer potential targets for treatment.
- Understanding the molecular landscape of both primary and recurrent glioblastomas is crucial for advancing clinical trial enrollment and treatment efficacy.
