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000298341 1001_ $$0P:(DE-He78)be724b82903aa397737196d8200edb30$$aWang, Changwen$$b0$$eFirst author
000298341 245__ $$aLaboratory-Engineered Glioblastoma Organoid Culture and Drug Screening.
000298341 260__ $$aCambridge, MA$$bJoVE$$c2025
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000298341 520__ $$aGlioblastoma (GBM) is described as a group of highly malignant primary brain tumors and stands as one of the most lethal malignancies. The genetic and cellular characteristics of GBM have been a focal point of ongoing research, revealing that it is a group of heterogeneous diseases with variations in RNA expression, DNA methylation, or cellular composition. Despite the wealth of molecular data available, the lack of transferable pre-clinic models has limited the application of this information to disease classification rather than treatment stratification. Transferring the patients' genetic information into clinical benefits and bridging the gap between detailed descriptions of GBM, genotype-phenotype associations, and treatment advancements remain significant challenges. In this context, we present an advanced human GBM organoid model, the Laboratory Engineered Glioblastoma Organoid (LEGO), and illustrate its use in studying the genotype-phenotype dependencies and screening potential drugs for GBM. Utilizing this model, we have identified lipid metabolism dysregulation as a critical milestone in GBM progression and discovered that the microsomal triglyceride transfer protein inhibitor Lomitapide shows promise as a potential treatment for GBM.
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000298341 650_2 $$2MeSH$$aGlioblastoma: genetics
000298341 650_2 $$2MeSH$$aGlioblastoma: pathology
000298341 650_2 $$2MeSH$$aHumans
000298341 650_2 $$2MeSH$$aOrganoids: metabolism
000298341 650_2 $$2MeSH$$aOrganoids: drug effects
000298341 650_2 $$2MeSH$$aBrain Neoplasms: genetics
000298341 650_2 $$2MeSH$$aBrain Neoplasms: pathology
000298341 650_2 $$2MeSH$$aDrug Screening Assays, Antitumor: methods
000298341 650_2 $$2MeSH$$aDrug Evaluation, Preclinical: methods
000298341 7001_ $$0P:(DE-He78)79d514e9270d1a0c8b17992db50542f1$$aStöffler, Nadja$$b1$$eFirst author$$udkfz
000298341 7001_ $$0P:(DE-He78)76aeb2431f7458c9261e69c5420390c6$$aLiu, Haikun$$b2$$eLast author$$udkfz
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