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A physiologically relevant glioma tumor model is important to the study of disease progression and screening drug candidates. However, current preclinical glioma models lack the brain microenvironment, and the established tumor cell lines do not represent glioma biology and cannot be used to evaluate the therapeutic effect. Here, we reported a real-time integrated system by generating 3D ex vivo cerebral organoids and in vivo xenograft tumors based on glioma patient-derived tissues and cells. Our system faithfully recapitulated the histological features, response to chemotherapy drugs, and clinical progression of their corresponding parental tumors. Additionally, our model successfully identified a case from a grade II astrocytoma patient with typical grade IV GBM features in both organoids and xenograft models, which mimicked the disease progression of this patient. Further genomic and transcriptomic …