BRG1-mediated suppression of ferroptosis underlies BTK inhibitor resistance.
Blocking a specific protein restores cancer cell death in lymphoma resistant to common drugs, pointing toward a combination therapy strategy.
Hwang et al. demonstrate that BRG1 (SMARCA4), a chromatin remodelling ATPase, suppresses ferroptotic cell death in B-cell lymphoma cells and enables tumour survival under BTK inhibitor pressure through chromatin-mediated transcriptional regulation of ferroptosis genes. Targeting the BRG1-ferroptosis axis sensitised mantle cell lymphoma and CLL cells to ferroptosis inducers in preclinical models, identifying a combination therapeutic strategy to overcome ibrutinib resistance.
What the study was
- Study design
- Mechanistic experimental study (in vitro and in vivo models)
- Population
- B-cell lymphoma experimental models (MCL and CLL cell lines and xenografts)
- Category
- Drug Development
- Maturity
- Exploratory
- Journal
- Nat Commun
Why it surfaced
Nature Communications study reveals novel chromatin-mediated resistance mechanism for BTK inhibitors in lymphoid malignancies; high translational potential for overcoming ibrutinib resistance.
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