Overcoming translational barriers in H3K27-altered diffuse midline glioma: Increasing the drug-tumor residence time.

ABSTRACT:

Background

H3K27-altered diffuse midline glioma (DMG) is the deadliest pediatric brain tumor; despite intensive research efforts, every clinical trial to date has failed. Is this because we are choosing the wrong drugs? Or are drug delivery and other pharmacokinetic variables at play? We hypothesize that the answer is likely a combination, where optimization may result in a much needed novel therapeutic approach.

Methods

We used in vitro drug screening, patient samples, and shRNA knockdown models to identify an upregulated target in DMG. A single small molecule protein kinase inhibitor with translational potential was selected for systemic and direct, loco-regional delivery to patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM). Pharmacokinetic st

SUBMITTER: Power EA 

PROVIDER: S-EPMC10148679 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature