Dataset Information

Dynamic Release of Exosomes After Opening of the Blood-Brain Barrier Predicts Glioblastoma Susceptibility to Paclitaxel

ABSTRACT: Liquid biopsies hold promise to improve the diagnosis, response to therapy, and ultimately guide the management of cancer patients, however implementation of this approach in brain tumors has proven challenging due to the limited passage of molecules across the blood-brain barrier (BBB). We recently reported results from a phase I clinical trial in which the BBB was transiently opened in glioblastoma (GBM) patients using skull-implantable low-intensity ultrasound combined with microbubbles (LIPU/MB), performed every 3 weeks with paclitaxel administration until disease progression (NCT04528680). Here, we investigate circulating exosomes, a potential biomarker for susceptibility to treatment, as an exploratory endpoint of this trial. After developing and validating a microfluidic device designed to capture tumor-specific exosomes in glioblastoma patients (GlioExoChip), we studied longitudinal changes in exosome concentrations during LIPU/MB-based BBB disruption and chemotherapy delivery. Exosomes were characterized using nanoparticle tracking analysis, proteomics, western blot, and scanning electron microscopy. GlioExoChip had high capture efficiency for GBM-specific exosomes with phosphatidylserine and Annexin-V chemistry. Longitudinal analysis of exosome changes after BBB opening correlated with MRI enhancement among patients. In vitro, paclitaxel-susceptible glioma cells treated with this drug exhibited apoptosis and exosome release. In concordance, we found changes in exosome release following initiation of paclitaxel with LIPU/MB correlated with overall survival in GBM patients. Our work presents an efficient microfluidic platform for capturing of circulating GBM exosomes , prospectively characterizes the release of tumor material after the opening of the BBB in a clinical trial , and demonstrates that longitudinal liquid biopsies can provide practical insights to improve the care of brain tumor patients

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

DISEASE(S): Brain Glioblastoma Multiforme

SUBMITTER: Abha Kumari

LAB HEAD: Abha Kumari

PROVIDER: PXD063771 | Pride | 2025-12-22

REPOSITORIES: Pride

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			Action	DRS
	PRF_A_2024_S_NAGR_1295_70308_70317_ZipTip_1_8.msf	Msf
	PRF_A_2024_S_NAGR_1295_70308_70317_ZipTip_1and5.raw	Raw
	PRF_A_2024_S_NAGR_1295_70308_70317_ZipTip_2and6.raw	Raw
	PRF_A_2024_S_NAGR_1295_70308_70317_ZipTip_3and7.raw	Raw
	PRF_A_2024_S_NAGR_1295_70308_70317_ZipTip_4and8.raw	Raw

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Publications

Dynamic release of extracellular particles after opening of the blood-brain barrier predicts glioblastoma susceptibility to paclitaxel.

Youngblood Mark W MW Kumari Abha A Kang Yoon-Tae YT Gould Andrew A Habashy Karl K Gomez Mateo M Lingamarla Harika H Morey Trevor T Chen Li L Congivaram Harrshavasan H Ward Rachel R Zhang Hui H Sears Thomas K TK McCortney Kathleen K Pituch Katarzyna C KC Torres Ponce Elena M EM Zarrieneh Ashkan A Nieves Mariana M Vandermolen Sarah S Primdahl Ditte D Dixit Karan K Lukas Rimas V RV Kumthekar Priya P Dmello Crismita C Bouchoux Guillaume G Canney Michael M Amidei Christina C Stupp Roger R Nagrath Sunitha S Sonabend Adam M AM

Nature communications 20251216 1

Liquid biopsies hold promise to improve the diagnosis, assessment of response to therapy, and ultimately guide the management of cancer patients. However, implementation of this approach in brain tumors has proven challenging due to the limited passage of molecules across the blood-brain barrier (BBB). We recently reported results from a phase I clinical trial in which the BBB was transiently opened in glioblastoma (GBM) patients using skull-implantable low-intensity pulsed ultrasound combined w ...[more]

PMID: 41402297

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