Related Experiment Video

Updated: Feb 13, 2026

Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures
06:32

Evaluation of Biomarkers in Glioma by Immunohistochemistry on Paraffin-Embedded 3D Glioma Neurosphere Cultures

Published on: January 9, 2019

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Functional genomics identifies therapeutic options, biomarkers, and resistance mechanisms for high-grade gliomas

Wan-Hsin Lin, Farhad Kosari, James B Smadbeck

    Biorxiv : the Preprint Server for Biology
    |February 12, 2026
    PubMed

    Insights

    This study explored personalized treatments for high-grade gliomas (HGGs) using 3D models. Combination therapies showed promise, identifying biomarkers and resistance mechanisms for improved HGG treatment strategies.

    Area of Science:

    • Oncology
    • Genomics
    • Pharmacology

    Background:

    • High-grade gliomas (HGGs) present significant challenges due to aggressive nature, poor prognoses, and limited therapeutic options.
    • Current treatment strategies for HGGs often lack efficacy, necessitating novel approaches for patient care.

    Purpose of the Study:

    • To identify individualized treatment strategies and predictive biomarkers for high-grade gliomas (HGGs).
    • To investigate drug sensitivity, resistance mechanisms, and effective combination therapies in HGGs using patient-derived models.

    Main Methods:

    • Combined genomic and transcriptomic profiling of patient-derived HGG tumors.
    • Utilized 3D culture models for ex vivo drug sensitivity testing of single agents and combinations.
    • Analyzed correlations between drug response, transcriptional features, and genomic alterations.

    Main Results:

    • Single agents showed limited efficacy, but PI3K, epigenetic, and survival/senescence pathway inhibitors were effective in select cases.
    • Drug sensitivity was linked to transcriptional profiles, with heterogeneity identified as a resistance mechanism.
    • Bromodomain and extraterminal domain inhibition showed efficacy in mesenchymal subtypes, while PI3K signaling impacted response.
    • Combination therapies demonstrated significantly higher efficacy than single agents in most tested strategies (58-77%).

    Conclusions:

    • Identified specific HGG vulnerabilities and potential biomarkers for targeted therapies.
    • Elucidated resistance mechanisms, including tumor heterogeneity and PI3K signaling.
    • Demonstrated the potential of combination therapies for improving HGG treatment outcomes, warranting clinical validation.

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