Abstract 3759: Single cell transcriptomics on a bioprinted 3D neurovascular unit glioblastoma model identifies pharmacological interventions that selectively target tumor cells

Abstract The tumor microenvironment (TME) is the cellular environment in which cancer cell exist and is made up of a combination of stroma cells and extra cellular matrix (ECM), secreted biomolecules, including cytokines, from both stroma cells and tumor cells. The TME composition drives tumor growth and drug resistance. We previously established a 96-wells based bioprinted glioblastoma (GBM) model that includes a neurovascular unit (NVU) made up of endothelial cells, astrocytes and pericytes. We demonstrated its applicability for drug screening by using high content imaging system to measure tumor size and vascular integrity. We then performed single cell RNA sequencing on this bioprinted NVU-GBM model. We used the single cell transcriptomics data to investigate ligand-receptor interactions between stroma and GBM cells, to find molecular pathways that potentially drive tumor growth and be targets for pharmacological intervention as anticancer drugs. We identified 50 ligand-receptors pairs and selected those with genes exclusively expressed in GBM cells but not in the stroma cells, to minimize potential toxic effects of drugs to the non-cancer cells. We performed a drug screen of 34 compounds targeting many of these receptors on the GBM cells, and identified 15 compounds that reduced GBM cells growth, with minimal effects on vascular integrity. This result demonstrates a promising pharmacogenomics approach to using bioengineered tumor growth tissue models that include the TME, integrated with single cell transcriptomics, to find actionable pharmacological targets that inhibit tumor growth without affecting the stroma cells. Citation Format: Yen-Ting Tung, Min Jae Song, Marc Ferrer. Single cell transcriptomics on a bioprinted 3D neurovascular unit glioblastoma model identifies pharmacological interventions that selectively target tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 3759.