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bioRxiv · 10.1101/2025.02.12.637574

StarTrace: A Multiplex Organoid Avatar Drug Testing Platform for Personalized Medicine

Khalili, S.·patel, S.·Patel, N.·Moy, V.·Lyons, S.·Gray, E.·Brents, R.·Banister, C. E.·Morrison, S. E.·Buckhaults, P. J.
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Abstract

The goal of precision medicine is to improve clinical outcomes of cancer patients by choosing treatments most likely to work. One idea is to match tumor response to cancer-causing somatic mutations, but this strategy still faces limitations in colorectal cancer due to poorly understood genetic influences on drug resistance. We describe here a simple direct drug sensitivity assay platform applied to mixtures of patient-derived organoid avatars as a practical solution for choosing therapy, sidestepping the need for exhaustive knowledge of drug-genetic interactions. This approach rank orders individual patient organoid avatars responses to various drugs to be used to guide treatment choices. The platform multiplexes organoids using a clonal barcoding method, called StarTrace, which simultaneously tests pools of multiple patients organoid avatars for sensitivity or resistance to small molecule inhibitors. We utilized both quantitative real-time PCR-based and single-molecule sequencing assays to track the relative Darwinian fitness of each barcoded organoid within the pool. StarTrace offers a rapid, cost effective and sensitive testing platform that could be useful for either preclinical drug development or tailoring personalized therapy.

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Khalili, S., patel, S., Patel, N., Moy, V., Lyons, S., Gray, E., Brents, R., Banister, C. E., Morrison, S. E., Buckhaults, P. J.. 2025-02-17. StarTrace: A Multiplex Organoid Avatar Drug Testing Platform for Personalized Medicine. https://doi.org/10.1101/2025.02.12.637574

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