Current status of precision oncology in adult glioblastoma
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 tu...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-12-01
|
| Series: | Molecular Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/1878-0261.13678 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1846140164698537984 |
|---|---|
| author | Johannes Weller Anna‐Laura Potthoff Thomas Zeyen Christina Schaub Cathrina Duffy Matthias Schneider Ulrich Herrlinger |
| author_facet | Johannes Weller Anna‐Laura Potthoff Thomas Zeyen Christina Schaub Cathrina Duffy Matthias Schneider Ulrich Herrlinger |
| author_sort | Johannes Weller |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-e9a4c9ccc168445b969bf1b09603be97 |
| institution | Kabale University |
| issn | 1574-7891 1878-0261 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Molecular Oncology |
| spelling | doaj-art-e9a4c9ccc168445b969bf1b09603be972024-12-05T17:48:54ZengWileyMolecular Oncology1574-78911878-02612024-12-0118122927295010.1002/1878-0261.13678Current status of precision oncology in adult glioblastomaJohannes Weller0Anna‐Laura Potthoff1Thomas Zeyen2Christina Schaub3Cathrina Duffy4Matthias Schneider5Ulrich Herrlinger6Department of Neurooncology, Center for Neurology University Hospital Bonn GermanyDepartment of Neurosurgery University Hospital Bonn GermanyDepartment of Neurooncology, Center for Neurology University Hospital Bonn GermanyDepartment of Neurooncology, Center for Neurology University Hospital Bonn GermanyDepartment of Neurooncology, Center for Neurology University Hospital Bonn GermanyDepartment of Neurosurgery University Hospital Bonn GermanyDepartment of Neurooncology, Center for Neurology University Hospital Bonn GermanyThe 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.https://doi.org/10.1002/1878-0261.13678biomarkerglioblastomamolecular profilingpersonalized medicineprecision oncologytargeted treatment |
| spellingShingle | Johannes Weller Anna‐Laura Potthoff Thomas Zeyen Christina Schaub Cathrina Duffy Matthias Schneider Ulrich Herrlinger Current status of precision oncology in adult glioblastoma Molecular Oncology biomarker glioblastoma molecular profiling personalized medicine precision oncology targeted treatment |
| title | Current status of precision oncology in adult glioblastoma |
| title_full | Current status of precision oncology in adult glioblastoma |
| title_fullStr | Current status of precision oncology in adult glioblastoma |
| title_full_unstemmed | Current status of precision oncology in adult glioblastoma |
| title_short | Current status of precision oncology in adult glioblastoma |
| title_sort | current status of precision oncology in adult glioblastoma |
| topic | biomarker glioblastoma molecular profiling personalized medicine precision oncology targeted treatment |
| url | https://doi.org/10.1002/1878-0261.13678 |
| work_keys_str_mv | AT johannesweller currentstatusofprecisiononcologyinadultglioblastoma AT annalaurapotthoff currentstatusofprecisiononcologyinadultglioblastoma AT thomaszeyen currentstatusofprecisiononcologyinadultglioblastoma AT christinaschaub currentstatusofprecisiononcologyinadultglioblastoma AT cathrinaduffy currentstatusofprecisiononcologyinadultglioblastoma AT matthiasschneider currentstatusofprecisiononcologyinadultglioblastoma AT ulrichherrlinger currentstatusofprecisiononcologyinadultglioblastoma |