Researchers reported novel Bruton tyrosine kinase (BTK) inhibitors that block invasion and progression in glioblastoma (GBM) models while offering improved selectivity relative to ibrutinib. The work shows selective BTK suppression reduces cancer stem cell–driven resistance and recurrence signals in preclinical studies. The findings underscore BTK’s non‑canonical role beyond hematologic malignancies and support development of CNS‑penetrant, selective inhibitors to avoid off‑target toxicities seen with first‑generation drugs. Translational steps will require CNS safety and pharmacokinetic profiling before clinical testing in GBM patients.