Exploring Novel Therapy in Pediatric Brain Tumor Using a High-Throughput Drug Screen Open Access

Abstract

Diffuse Intrinsic Pontine Glioma (DIPG) is an aggressive pediatric brain tumor arising in the pons region of the brainstem that is characterized by its diffuse infiltration, resistance to conventional chemotherapies, and extremely poor prognosis. Median survival remains less than one year, underscoring the urgent need for new therapeutic strategies. However, the challenges of drug delivery across the blood-brain barrier and the rarity of the disease complicate the development of effective treatments. Therefore, this thesis focuses on repurposing existing central nervous system (CNS) penetrant drug compounds as potential therapeutic agents for DIPG. Using a high-throughput drug screening approach, a library of 788 clinically relevant compounds with known CNS bioavailability was evaluated for their ability to inhibit DIPG cell viability. To better assess drug efficacy in a physiologically relevant context, an ex vivo organotypic brain slice model was optimized to evaluate drug responses in an environment that mimics in vivo tumor-brain interactions, thereby bridging the gap between traditional cell culture assays and in vivo models. From this study, we have identified 11 drug candidates to further examine in ex vivo organoid models and in vivo mouse models of DIPG, and we highlight several potential target pathways for ongoing DIPG research.

Table of Contents

Abstract - pg 1

Introduction - pg 1

Materials and Methods - pg 2

Results - pg 3

Discussion - pg 5

Conclusion - pg 16

Acknowledgements - pg 17

Figure - pg 18

References - pg 31

About this Master's Thesis

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• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Laney Graduate School
Department	Biological and Biomedical Sciences
Subfield / Discipline	Cancer Biology
Degree	M.S.
Submission	Master's Thesis
Language	English
Research Field	Biology, Cell
Keyword	DIPG
Committee Chair / Thesis Advisor	Biplab Dasgupta, Emory University

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