4.8 Article

A pan-cancer organoid platform for precision medicine

期刊

CELL REPORTS
卷 36, 期 4, 页码 -

出版社

CELL PRESS
DOI: 10.1016/j.celrep.2021.109429

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资金

  1. Rush University Medical Center
  2. Swim Across America Foundation
  3. University of Chicago Comprehensive Cancer Center (UCCCC) Award in Precision Oncology-Cancer Center Support Grant [P30CA014599]
  4. UCCCC Ullman Scholar Award for immunotherapy

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A robust pan-cancer tumor organoid platform with chemically defined media has been established and neural-network-based high-throughput method has been demonstrated to predict patient-specific heterogeneity in drug responses. These resources are expected to accelerate the broad implementation of organoid models in precision medicine research and personalized therapeutic profiling programs.
Patient-derived tumor organoids (TOs) are emerging as high-fidelity models to study cancer biology and develop novel precision medicine therapeutics. However, utilizing TOs for systems-biology-based approaches has been limited by a lack of scalable and reproducible methods to develop and profile these models. We describe a robust pan-cancer TO platform with chemically defined media optimized on cultures acquired from over 1,000 patients. Crucially, we demonstrate tumor genetic and transcriptomic concordance utilizing this approach and further optimize defined minimal media for organoid initiation and propagation. Additionally, we demonstrate a neural-network-based high-throughput approach for label-free, light-microscopy-based drug assays capable of predicting patient-specific heterogeneity in drug responses with applicability across solid cancers. The pan-cancer platform, molecular data, and neural-network-based drug assay serve as resources to accelerate the broad implementation of organoid models in precision medicine research and personalized therapeutic profiling programs.

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