Glioma invasion assays as a predictive tool for personalized glioma medicine

Glioblastoma multiforme is the most common malignant brain tumor. The median survival of patients is less than 24 months, and there is currently no cure. There are significant limitations for glioblastoma therapeutics. Particularly, glioblastoma are highly heterogeneous and unique for each patient, preventing "one therapy for all." In "Glioma-PerMed" project, we will establish rapid and efficient assays and machine learning algorithms to predict the invasive properties of glioma and achieve personalized diagnostics, drug discovery, and patient follow-up. We will assess the invasion properties of glioma cells in brain organoids, which are 3D in vitro systems of human brain tissues, and in the zebrafish animal model. We will develop quantitative analyses to measure the invasion behavior of glioblastoma cells and correlate to their genomic and transcriptomic landscape. We will also screen for drugs with the goal to identify molecules that can quickly be transferred to GBM patients in the clinics.

Glioblastoma multiforme (GBM) is the most frequent malignant brain tumor. GBM possesses glioma stem cells (GSCs) that aggressively infiltrate the brain. GBM patients' median survival is <24 months, and there is no cure. There are also significant bottlenecks that currently limit GBM therapeutics: GBMs are highly heterogeneous and unique for each patient, preventing "one therapy for all." , and GSCs are highly diffusive from the tumour and invade the brain rapidly and unpredictably. In "Glioma-PerMed", we will establish rapid and efficient glioma invasion assays and machine learning algorithms to predict the GSCs invasion and achieve personalized diagnostics, drug discovery, and patient follow-up. To this end, it is necessary to develop suitable models that recapitulate the complex human brain environment and translate into clinical application. 3D brain organoids, powerful in vitro systems of human brain tissues and emerging as a 3D substrate to model glioma, will be a centerpiece of this project. Building on our established patient-derived GSCs invasion assay in human brain organoids, we propose a highly interdisciplinary and translational research project, "Glioma-PerMed", to develop personalized glioma invasion assays in human brain organoids and zebrafish. We will quantitatively determine the GSCs invasion behaviors and correlate to their genomic and transcriptomic landscape with unbiased machine learning algorithms to stratify patients. Our "personalized glioma invasion" platform will also offer to screen FDA-approved drug libraries and identify molecules that can readily and quickly be transferred to GBM patients in the clinics. By inventing a strategy that can rapidly recapitulate the invasion behaviour of GSCs in individual patients, we will stratify GBM patient groups and identify patient-specific therapeutic molecules that can perturb GSCs invasions in clinical settings. Ultimately, our work will be the first step towards personalized GBM medicine.