Related Experiment Video
Updated: Jun 25, 2026
Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
Current status of precision oncology in adult glioblastoma
Johannes Weller1, Anna-Laura Potthoff2, Thomas Zeyen1
1Department of Neurooncology, Center for Neurology, University Hospital Bonn, Germany.
Abstract:
The concept of precision oncology, the application of targeted drugs based on comprehensive molecular profiling, has revolutionized treatment strategies in oncology. This review summarizes the current status of precision oncology in glioblastoma (GBM), the most common and aggressive primary brain tumor in adults with a median survival below 2 years. Targeted treatments without prior target verification have consistently failed. Patients with BRAF V600E-mutated GBM benefit from BRAF/MEK-inhibition, whereas targeting EGFR alterations was unsuccessful due to poor tumor penetration, tumor cell heterogeneity, and pathway redundancies. Systematic screening for actionable molecular alterations resulted in low rates (< 10%) of targeted treatments. Efficacy was observed in one-third and currently appears to be limited to BRAF-, VEGFR-, and mTOR-directed treatments. Advancing precision oncology for GBM requires consideration of pathways instead of single alterations, new trial concepts enabling rapid and adaptive drug evaluation, a focus on drugs with sufficient bioavailability in the CNS, and the extension of target discovery and validation to the tumor microenvironment, tumor cell networks, and their interaction with immune cells and neurons.
Insights
Precision oncology in glioblastoma (GBM) shows limited success, with targeted treatments benefiting only a subset of patients. Future strategies require pathway-focused approaches and improved drug delivery to the central nervous system (CNS).
Area of Science:
- Neuro-oncology
- Molecular Oncology
- Translational Medicine
Background:
- Glioblastoma (GBM) is an aggressive brain tumor with poor prognosis.
- Precision oncology aims to personalize cancer treatment using molecular profiling.
- Current targeted therapies in GBM have shown limited efficacy.
Purpose of the Study:
- To review the current status of precision oncology in glioblastoma.
- To identify successes and challenges of targeted therapies in GBM.
- To propose future directions for advancing precision oncology in GBM.
Main Methods:
- Review of existing literature on precision oncology in GBM.
- Analysis of clinical trial data for targeted therapies in GBM.
- Evaluation of molecular alterations and their therapeutic implications.
Main Results:
- Targeted treatments without prior target verification have largely failed.
- BRAF V600E-mutated GBM shows benefit from BRAF/MEK inhibition.
- EGFR targeting has been unsuccessful due to biological challenges.
- Systematic screening yields low rates of actionable targets (<10%).
- Efficacy observed in one-third of patients, mainly with BRAF, VEGFR, and mTOR inhibitors.
Conclusions:
- Advancing precision oncology in GBM necessitates a shift from single alterations to pathway-based strategies.
- New clinical trial designs are needed for rapid, adaptive drug evaluation.
- Focus on drugs with adequate central nervous system (CNS) bioavailability is crucial.
- Expanding target discovery to include the tumor microenvironment, cell networks, and immune interactions is essential.
Related Concept Videos
02:56Treatment Resistant Cancers
02:56Treatment Resistent Cancers