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Updated: Jan 17, 2026

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics
04:01

Author Spotlight: Tracing the Ferroptotic Signatures and Cell Death Dynamics in Medulloblastoma for Advanced Therapeutics

Published on: March 15, 2024

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Leveraging BRG1 Driven Ferroptosis Resistance to Overcome Treatment Resistance

Soo-Yeon Hwang, Helgi Nikolli, Belem Yoval-Sánchez

    Biorxiv : the Preprint Server for Biology
    |September 15, 2025
    PubMed

    Insights

    Bruton

    Area of Science:

    • Oncology
    • Molecular Biology
    • Cancer Research

    Background:

    • Bruton's tyrosine kinase inhibitors (BTKi) are crucial for treating B-cell malignancies.
    • Therapeutic resistance to BTKi limits treatment effectiveness and durability.
    • Understanding resistance mechanisms is vital for improving patient outcomes.

    Purpose of the Study:

    • To investigate the mechanisms underlying BTKi resistance in mantle cell lymphoma (MCL).
    • To identify novel therapeutic targets for overcoming BTKi resistance.

    Main Methods:

    • Investigated ferroptosis suppression as a resistance mechanism.
    • Analyzed the role of BRG1 (BRG1-associated factor 1) in regulating ferroptosis.
    • Examined BTK-dependent and independent signaling pathways.
    • Utilized pharmacologic inhibition of BRG1 in MCL models.

    Main Results:

    • Ferroptosis suppression is a key mechanism of BTKi resistance in MCL.
    • Aberrant BRG1 activity protects MCL cells from ferroptosis by limiting reactive oxygen species (ROS) and labile iron.
    • BRG1 promotes resistance via BTK-dependent survival and a BTK-independent transcriptional program involving MEF2B and NDUFA4L2.
    • BRG1 inhibition restores ferroptosis sensitivity and synergizes with BTKi.

    Conclusions:

    • BRG1 is a central regulator of BTKi resistance in B-cell malignancies.
    • Co-targeting BRG1 and BTK presents a promising therapeutic strategy for resistant MCL.

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