Glioblastoma (GBM) remains one of the most treatment-resistant brain cancers: the blood?brain barrier (BBB) and blood?tumor barrier (BTB) severely limit chemotherapy penetration. A new study published in Science Advances (February 26, 2025) addresses this challenge by identifying a 12-gene transcriptional signature associated with the BTB in GBM—and highlights CDH5 as a central regulator X-MOL+2X-MOL+2.
The researchers discovered that the compound 6- bromoindirubin acetoxime (BIA) down-regulates CDH5 and other BTB marker genes, leading to controlled disruption of endothelial barriers in vitro and in mouse GBM models. This disruption facilitates increased cisplatin accumulation in tumors and heightened DNA damage. When formulated into nanoparticles (PPRX?1701), BIA delivers these benefits in vivo, significantly enhancing cisplatin efficacy in GBM xenografts Europe PMC+4X-MOL+4X-MOL+4.
Why it matters:
Novel mechanism: Transcriptional modulation of BTB to improve drug access.
Dual role compound: BIA both weakens barrier and potentiates chemotherapy.
Translational potential: Nanoparticle delivery system shows strong preclinical efficacy.
This research unveils promising targets and strategies for overcoming one of neuro-oncology’s toughest barriers: bringing lifesaving chemotherapies into GBM tumors.