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Drug-delivering particles aim to breach the blood–brain barrier
Nanoparticle- and exosome-based drug delivery platforms are advancing as strategies to overcome the blood–brain barrier, a decades-old obstacle to treating brain tumours and neurodegenerative diseases. Nature reviews competing approaches that aim to ferry therapeutics across the barrier selectively, potentially improving outcomes for gliomas and other CNS malignancies. No single technique has yet …
Temozolomide Versus Radiotherapy as First-Line Treatment for Low-Grade Glioma
Mature results of the phase 3 EORTC 22033-26033 trial (n=478) showed NO difference between temozolomide and radiotherapy as first-line therapy for high-risk low-grade glioma, in either progression-free or overall survival, regardless of molecular subtype. In IDH-mutant, 1p/19q non-codeleted astrocytoma (n=178) median overall survival was similar in both arms (6.6-6.7 years; P=.93), and in 1p/19q c…
The critical role of the endogenous immune compartment after CAR T cell therapy in recurrent GBM
Profiling of cerebrospinal fluid and tumour samples from patients in a phase 1 trial (NCT05168423) of intracerebroventricular CAR T cells for recurrent glioblastoma indicates that outcomes were defined by remodelling of the patient's own immune landscape rather than by CAR T activation alone, which occurred in every treated patient. Responders were characterised by expansion of cytotoxic natural k…
Exploring the landscape of targetable alterations in patients with glioblastoma
A comprehensive review in Nature Reviews Clinical Oncology maps the landscape of targetable molecular alterations in glioblastoma and examines why prior targeted therapy approaches have largely failed. The authors identify key challenges, including blood-brain barrier penetrance, intra-tumoral heterogeneity, and redundant signaling pathways, that have limited clinical progress despite advances in …
Brain barriers at the crossroads of glioma immune surveillance and immunotherapy response
A comprehensive review in Nature Reviews Cancer by Engelhardt and Platten delineates how specialized brain barriers enforce central nervous system immune privilege, severely restricting T cell surveillance and rendering immunotherapy largely ineffective in gliomas. The authors systematically catalog the cellular and molecular mechanisms by which the blood-brain barrier, blood-CSF barrier, and meni…