PDX model in zebrafish to understand the role of BBB modulation on tumor treatments

The purpose of this study is to develop a zebrafish-based in vivo platform for personalized glioblastoma (GBM) therapy assessment. By engrafting patient-derived GBM biopsies into the zebrafish brain, we aim to:

1. Identify the most effective available therapeutic regimen to reduce tumor burden for each individual patient.
2. Evaluate the impact of blood-brain barrier (BBB) modulating agents on chemotherapeutic delivery and efficacy in vivo on an individual tumor level.

This approach will allow us to rapidly test and compare treatment responses in a live vertebrate brain with a fully functional BBB, offering a potentially translational strategy for individualized GBM treatment decisions and advancing understanding of how BBB-targeted therapies influence tumor response and overall survival.

Objectives:
1. To generate zebrafish patient-derived xenograft (PDX) models by implanting freshly resected glioblastoma tumor tissue into the zebrafish brain. This will allow us to study patient-specific tumor biology in a live vertebrate system.

2. To evaluate the efficacy of standard-of-care and other clinically available chemotherapeutic agents in reducing tumor burden in each zebrafish PDX model. The goal is to determine which treatment, or combination of treatments, is most effective for that patient s particular brain tumor.

3. To investigate the impact of BBB modulating compounds on drug delivery and therapeutic efficacy in the intact zebrafish brain. This includes assessing whether such modulation improves tumor suppression or, conversely, affects tumor progression or host toxicity.

4. To develop a rapid, in vivo screening platform that integrates tumor response and BBB dynamics, with the ultimate aim of informing personalized treatment decisions for glioblastoma patients within a few weeks following surgery.

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