Convection-Enhanced Delivery of Enhancer of Zeste Homolog-2 (EZH2) Inhibitor for the Treatment of Diffuse Intrinsic Pontine Glioma.

Neurosurgery
Takahiro SasakiRintaro Hashizume

Abstract

Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood brain tumor and the majority of patients die within 2 yr after initial diagnosis. Factors that contribute to the dismal prognosis of these patients include the infiltrative nature and anatomic location in an eloquent area of the brain, which precludes total surgical resection, and the presence of the blood-brain barrier (BBB), which reduces the distribution of systemically administered agents. Convection-enhanced delivery (CED) is a direct infusion technique to deliver therapeutic agents into a target site in the brain and able to deliver a high concentration drug to the infusion site without systemic toxicities. To assess the efficacy of enhancer of zeste homolog-2 (EZH2) inhibitor by CED against human DIPG xenograft models. The concentration of EZH2 inhibitor (EPZ-6438) in the brainstem tumor was evaluated by liquid chromatography-mass spectrometry (LC/MS). We treated mice-bearing human DIPG xenografts with EPZ-6438 using systemic (intraperitoneal) or CED administration. Intracranial tumor growth was monitored by bioluminescence image, and the therapeutic response was evaluated by animal survival. LC/MS analysis showed that the concentration of EPZ-6438 in the brain...Continue Reading

Citations

Mar 23, 2021·BioMed Research International·Quintino Giorgio D'AlessandrisRoberto Pallini

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