A pan-cancer organoid platform for precision medicine

Brian M. Larsen, Madhavi Kannan, Lee F. Langer, Benjamin D. Leibowitz, Aicha Bentaieb, Andrea Cancino, Igor Dolgalev, Bridgette E. Drummond, Jonathan R. Dry, Chi Sing Ho, Gaurav Khullar, Benjamin A. Krantz, Brandon Mapes, Kelly E. McKinnon, Jessica Metti, Jason F. Perera, Tim A. Rand, Veronica Sanchez-Freire, Jenna M. Shaxted, Michelle M. SteinMichael A. Streit, Yi Hung Carol Tan, Yilin Zhang, Ende Zhao, Jagadish Venkataraman, Martin C. Stumpe, Jeffrey A. Borgia, Ashiq Masood, Daniel V.T. Catenacci, Jeremy V. Mathews, Demirkan B. Gursel, Jian Jun Wei, Theodore H. Welling, Diane M. Simeone, Kevin P. White, Aly A. Khan*, Catherine Igartua, Ameen A. Salahudeen

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Article number109429
JournalCell reports
Volume36
Issue number4
DOIs
StatePublished - Jul 27 2021

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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