1. A pan-cancer organoid platform for precision medicine
- Author
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Theodore H. Welling, Diane M. Simeone, Benjamin A. Krantz, Aïcha BenTaieb, Andrea Cancino, Chi Sing Ho, Jeffrey A. Borgia, Jeremy V. Mathews, Brandon Mapes, Michael A. Streit, Jian Jun Wei, Ameen A. Salahudeen, Bridgette E. Drummond, Veronica Sanchez-Freire, Martin C. Stumpe, Aly A. Khan, Tim A. Rand, Ende Zhao, Kelly E. McKinnon, Benjamin D. Leibowitz, Demirkan B. Gursel, Madhavi Kannan, Jagadish Venkataraman, Yi-Hung Carol Tan, Brian M. Larsen, Jonathan R. Dry, Gaurav Khullar, Jenna M. Shaxted, Catherine Igartua, Kevin P. White, Daniel V.T. Catenacci, Ashiq Masood, Jason Perera, Jessica Metti, Michelle M. Stein, Igor Dolgalev, Lee F. Langer, and Yilin Zhang
- Subjects
Male ,Computer science ,QH301-705.5 ,Loss of Heterozygosity ,Computational biology ,Models, Biological ,General Biochemistry, Genetics and Molecular Biology ,Fluorescence ,HLA Antigens ,Neoplasms ,Organoid ,Humans ,Cancer biology ,Biology (General) ,Precision Medicine ,Cell Proliferation ,Pan cancer ,Genomics ,Middle Aged ,Precision medicine ,Drug assay ,Organoids ,Female ,Neural Networks, Computer ,Drug Screening Assays, Antitumor ,Transcriptome - Abstract
Summary: 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.
- Published
- 2020