Project description:We introduce OncoLoop, a highly-generalizable, precision medicine framework to triangulate between available mouse models, human tumors, and large-scale drug perturbational assays with in vivo validation to predict personalized treatment
Project description:Embryonal brain tumors (EBTs), arising during early brain development, present significant challenges in understanding pathogenesis and developing treatments. This study explores the efficacy of forebrain organoid models in replicating the complexities of the EBT microenvironment. We established an EBT-forebrain-organoid (EBT-FBO) model, incorporating embryonal tumor with multilayered rosettes (ETMR) and atypical teratoid and rhabdoid tumor (ATRT), using a scalable liquid-handling-assisted coaggregation method. Comprehensive characterization, including wholemount immunostaining, immunohistochemistry, single-cell RNA sequencing, integration with existing datasets, and automated cell-type-specific drug screening, validated the EBT-FBO model. EBT-FBOs closely mimicked mid-gestational fetal brain environments, with EBTs reflecting intratumoral heterogeneity at both histological and transcriptomic levels. Drug screening on ETMR-FBOs identified promising treatment options, including anthracyclins and Triptolide, which demonstrated anti-tumoral effects with minimal neurotoxicity. Scalable EBT-FBO models that resemble immature neuronal microenvironments similar to ETMR or ATRT mark significant progress towards targeted therapy and personalized precision medicine that requires recapitulation of individual tumor heterogeneities.
Project description:Embryonal brain tumors (EBTs), arising during early brain development, present significant challenges in understanding pathogenesis and developing treatments. This study explores the efficacy of forebrain organoid models in replicating the complexities of the EBT microenvironment. We established an EBT-forebrain-organoid (EBT-FBO) model, incorporating embryonal tumor with multilayered rosettes (ETMR) and atypical teratoid and rhabdoid tumor (ATRT), using a scalable liquid-handling-assisted coaggregation method. Comprehensive characterization, including wholemount immunostaining, immunohistochemistry, single-cell RNA sequencing, integration with existing datasets, and automated cell-type-specific drug screening, validated the EBT-FBO model. EBT-FBOs closely mimicked mid-gestational fetal brain environments, with EBTs reflecting intratumoral heterogeneity at both histological and transcriptomic levels. Drug screening on ETMR-FBOs identified promising treatment options, including anthracyclins and Triptolide, which demonstrated anti-tumoral effects with minimal neurotoxicity. Scalable EBT-FBO models that resemble immature neuronal microenvironments similar to ETMR or ATRT mark significant progress towards targeted therapy and personalized precision medicine that requires recapitulation of individual tumor heterogeneities.
Project description:Embryonal brain tumors (EBTs), arising during early brain development, present significant challenges in understanding pathogenesis and developing treatments. This study explores the efficacy of forebrain organoid models in replicating the complexities of the EBT microenvironment. We established an EBT-forebrain-organoid (EBT-FBO) model, incorporating embryonal tumor with multilayered rosettes (ETMR) and atypical teratoid and rhabdoid tumor (ATRT), using a scalable liquid-handling-assisted coaggregation method. Comprehensive characterization, including wholemount immunostaining, immunohistochemistry, single-cell RNA sequencing, integration with existing datasets, and automated cell-type-specific drug screening, validated the EBT-FBO model. EBT-FBOs closely mimicked mid-gestational fetal brain environments, with EBTs reflecting intratumoral heterogeneity at both histological and transcriptomic levels. Drug screening on ETMR-FBOs identified promising treatment options, including anthracyclins and Triptolide, which demonstrated anti-tumoral effects with minimal neurotoxicity. Scalable EBT-FBO models that resemble immature neuronal microenvironments similar to ETMR or ATRT mark significant progress towards targeted therapy and personalized precision medicine that requires recapitulation of individual tumor heterogeneities.
Project description:Embryonal brain tumors (EBTs), arising during early brain development, present significant challenges in understanding pathogenesis and developing treatments. This study explores the efficacy of forebrain organoid models in replicating the complexities of the EBT microenvironment. We established an EBT-forebrain-organoid (EBT-FBO) model, incorporating embryonal tumor with multilayered rosettes (ETMR) and atypical teratoid and rhabdoid tumor (ATRT), using a scalable liquid-handling-assisted coaggregation method. Comprehensive characterization, including wholemount immunostaining, immunohistochemistry, single-cell RNA sequencing, integration with existing datasets, and automated cell-type-specific drug screening, validated the EBT-FBO model. EBT-FBOs closely mimicked mid-gestational fetal brain environments, with EBTs reflecting intratumoral heterogeneity at both histological and transcriptomic levels. Drug screening on ETMR-FBOs identified promising treatment options, including anthracyclins and Triptolide, which demonstrated anti-tumoral effects with minimal neurotoxicity. Scalable EBT-FBO models that resemble immature neuronal microenvironments similar to ETMR or ATRT mark significant progress towards targeted therapy and personalized precision medicine that requires recapitulation of individual tumor heterogeneities.
Project description:Embryonal brain tumors (EBTs), arising during early brain development, present significant challenges in understanding pathogenesis and developing treatments. This study explores the efficacy of forebrain organoid models in replicating the complexities of the EBT microenvironment. We established an EBT-forebrain-organoid (EBT-FBO) model, incorporating embryonal tumor with multilayered rosettes (ETMR) and atypical teratoid and rhabdoid tumor (ATRT), using a scalable liquid-handling-assisted coaggregation method. Comprehensive characterization, including wholemount immunostaining, immunohistochemistry, single-cell RNA sequencing, integration with existing datasets, and automated cell-type-specific drug screening, validated the EBT-FBO model. EBT-FBOs closely mimicked mid-gestational fetal brain environments, with EBTs reflecting intratumoral heterogeneity at both histological and transcriptomic levels. Drug screening on ETMR-FBOs identified promising treatment options, including anthracyclins and Triptolide, which demonstrated anti-tumoral effects with minimal neurotoxicity. Scalable EBT-FBO models that resemble immature neuronal microenvironments similar to ETMR or ATRT mark significant progress towards targeted therapy and personalized precision medicine that requires recapitulation of individual tumor heterogeneities.
Project description:Embryonal brain tumors (EBTs), arising during early brain development, present significant challenges in understanding pathogenesis and developing treatments. This study explores the efficacy of forebrain organoid models in replicating the complexities of the EBT microenvironment. We established an EBT-forebrain-organoid (EBT-FBO) model, incorporating embryonal tumor with multilayered rosettes (ETMR) and atypical teratoid and rhabdoid tumor (ATRT), using a scalable liquid-handling-assisted coaggregation method. Comprehensive characterization, including wholemount immunostaining, immunohistochemistry, single-cell RNA sequencing, integration with existing datasets, and automated cell-type-specific drug screening, validated the EBT-FBO model. EBT-FBOs closely mimicked mid-gestational fetal brain environments, with EBTs reflecting intratumoral heterogeneity at both histological and transcriptomic levels. Drug screening on ETMR-FBOs identified promising treatment options, including anthracyclins and Triptolide, which demonstrated anti-tumoral effects with minimal neurotoxicity. Scalable EBT-FBO models that resemble immature neuronal microenvironments similar to ETMR or ATRT mark significant progress towards targeted therapy and personalized precision medicine that requires recapitulation of individual tumor heterogeneities.