# Rapid Functional Drug Screening of Passage-Zero Patient Brain Tumor Tissues Ex Vivo: Results from a Clinical Feasibility Study

## TL;DR

A new platform called SLiCE enables rapid drug testing on patient brain tumor tissues, showing promise for personalized treatment and drug development.

## Contribution

SLiCE is a novel ex vivo drug screening platform that preserves tumor characteristics and enables functional precision medicine in neuro-oncology.

## Key findings

- SLiCE successfully engrafted and tested 35 of 36 diverse brain tumor specimens within four days.
- SLiCE DSSs correlated with patient response to temozolomide and overall survival in IDH-WT glioblastoma.
- Surgically aspirated tumor tissue proved a viable and abundant source for SLiCE testing.

## Abstract

Functional precision medicine (FPM) offers a promising path forward in neuro-oncology, where genomic profiling alone often fails to predict therapeutic response. To bridge this gap, we developed the Screening Live Cancer Explants (SLiCE) platform, a rapid ex vivo drug screening assay that functionally tests passage-zero patient brain tumor tissues engrafted atop living organotypic brain slice cultures (OBSCs). With an assay time of just four days, SLiCE preserves key tumor characteristics not maintained in vitro, including genomic fidelity, growth, invasion, and treatment response, with higher engraftment rates and faster assay speeds than in vivo models. Our standard cryopreservation workflow enables reproducible, iterative, and on-demand testing of a single zero-passage specimen banked in multiple replicate aliquots, setting SLiCE apart from organoid and precision-cut tumor explant models. Here, we describe results from our actively accruing clinical feasibility study (NCT05978557), where we successfully engrafted and tested 35 of 36 diverse brain tumor specimens on SLiCE, achieving our study’s primary endpoint ahead of schedule. SLiCE produced multi-parametric drug sensitivity scores (DSSs), each normalized to off-target toxicity, for all samples within a clinically actionable 28-day window. Across 530 experiments, we generated 142 DSSs from unique drug-tumor combinations, forming a reference library for future benchmarking. We then further analyzed a subset of IDH-WT glioblastoma tumor specimens in which SLiCE DSSs correlated with patient response to temozolomide (AUC = 0.875, p = 0.0175) and overall survival (R2 = 0.73). Additionally, this study validated surgically aspirated tumor tissue as a genomically, transcriptomically, and functionally similar tumor source compared to the standard, manually excised remnant tumor sample approved by clinical pathology. Collecting this often-discarded tumor source increased the mass of tumors accrued by nearly 5-fold and enabled collection from 11 additional patients, significantly increasing tumor tissue for downstream testing on SLiCE. These findings establish SLiCE as a scalable, clinically relevant platform for FPM in brain cancer, with potential to guide individualized treatment decisions and accelerate preclinical drug development.