BIOM-16. A MULTI-OMIC, FUNCTIONAL PRECISION ONCOLOGY METHOD TO IDENTIFY RESPONSIVE GLIOBLASTOMA TUMOR CELLS AT SINGLE CELL RESOLUTION. (14th November 2022)

• Record Type: Journal Article
• Authors: De Visser, Yanti; Panovska, Dena; Cole, Basiel; Hermans, Lotte; Martinez, Asier Antoranz; Nazari, Pouya; Van Trimpont, Maaike; Derweduwe, Marleen; Claeys, Annelies; De Vleeschouwer, Steven; Solie, Lien; Clement, Paul; Sciot, Raf; Verfaillie, Michiel; Daenekindt, Thomas; Bamps, Sven; Van Vlierberghe, Pieter; De Smet, Frederik
• Is Part Of: Neuro-oncology. Volume 24(2022)Supplement 7
• Page Start: vii7
• Page End: vii7
• Publication Date: 2022-11-14
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noac209.026
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Glioblastoma remains a highly malignant and intrinsically resistant brain tumor. Despite intensive research through which numerous potential druggable targets were identified, virtually all clinical trials of the past 20 years failed to improve the outcome for the vast majority of GBM patients. However, the identification of small subgroups of patients that showed an exceptional response across several trials, implies that, when selected more carefully, some GBM patients could probably still benefit from these therapies. Identifying these patients requires that suitable biomarkers are identified. In this project, we reassessed the molecular mechanisms of ten actionable compounds (selected from previously failed trials but for which exceptional responders had been observed) in a set of carefully selected patient-derived cell lines that were sensitive/resistant to the selected therapies. Moreover, to deal with tumor heterogeneity, we used a multi-omic functional precision oncology approach, combining scRNA-seq and CyTOF, to identify drug-specific biomarkers by comparing control and treated samples at single-cell resolution. By subsequently correlating the molecular signatures to eventual cytotoxicity profiles, we could identify intrinsically responsive tumor cells at the single-cell level within hours following drug exposure. Overall, this work lays the foundation for an actionable functional diagnostic assay that could help to identify eligible GBM patients in future clinical trials.