DDRE-42. TOWARDS PRECISION MEDICINE: AUTOMATED DRUG SCREENING PLATFORM UTILIZING TUMOR-ORGANOIDS TO IDENTIFY PATIENT-SPECIFIC DRUG-RESPONSES IN MENINGIOMA

Abstract

Abstract Tumor-organoids (TO) are mini-tumors generated from tumor tissue preserving its genotype and phenotype by maintaining the cellular heterogeneity and important components of the tumor microenvironment. We recently developed a protocol to reliably establish TOs from meningioma (MGM) in large quantities. The use of TOs in combination with lab automation holds great promise for drug discovery and screening of comprehensive drug libraries. This might help to tailor patient-specific therapy in the future. The aim of our study was to establish an automated drug screening platform utilizing TOs. For this purpose, we established TOs by controlled reaggregation of freshly prepared single cell suspension of MGM tissue samples in the high-throughput format of 384-well plates. The drug screening was performed fully automated by utilizing the robotic liquid handler Hamilton Microlab STAR and a drug library containing 166 FDA-approved oncology agents. Viability was assessed with CellTiterGlo3D. In total, we performed the drug screening with 166 drugs on TOs from 11 patients suffering from MGM (n=8 WHO°I, n=2 WHO°II, n=1 WHO°III). The top five most effective drugs resulted in a decrease of TO viability ranging from 84.6–63.3%. K-means clustering analysis resulted in groupings of drugs with similar modes of action. One cluster consisted of epigenetic drugs while another cluster consisted of several proteasome inhibitors. However, when looking at a patient-individual level, in 11 patients 44 of 166 drugs, were among the top 10 most effective drugs, providing strong evidence for heterogeneous drug-responses in MGM patients. Taken together, we successfully developed an automated drug screening platform pipeline utilizing TOs from MGM to identify patient-specific drug-responses. The observed intra-individual differences of drug responses mandate for a personalized testing of comprehensive drug libraries in TOs to tailor more effective therapies in MGM patients.