Journal
NATURE BIOTECHNOLOGY
Volume 34, Issue 11, Pages 1161-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.3697
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Funding
- US National Institutes of Health [R01 CA170592, P50 CA165962, P01 CA112536, R33 CA191113]
- National Cancer Institute [U54 CA143874, P30 CA14051, T32 CA009172]
- Koch Institute for Integrative Cancer Research at MIT
- Dana-Farber/Harvard Cancer Center (DF/HCC)
- Dana-Farber Cancer Institute Brain Tumor Therapeutics Accelerator Program
- Vondation ARC pour la Recherche sur le Cancer
- Institut Universitaire de Cancerologie
- Onco Neuro Theque
- program Investissements d'aveniC [ANR-10-IAIHU-06]
- NIHNIGMS [T32 GM008334]
- Interdepartmental Biotechnology Training Program grant
- National Science Scholarship, Agency for Science, Technology and Research (STAR), Singapore
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Assays that can determine the response of tumor cells to cancer therapeutics could greatly aid the selection of drug regimens for individual patients. However, the utility of current functional assays is limited, and predictive genetic biomarkers are available for only a small fraction of cancer therapies. We found that the single-cell mass accumulation rate (MAR), profiled over many hours with a suspended microchannel resonator, accurately defined the drug sensitivity or resistance of glioblastoma and B-cell acute lymphocytic leukemia cells. MAR revealed heterogeneity in drug sensitivity not only between different tumors, but also within individual tumors and tumor-derived cell lines. MAR measurement predicted drug response using samples as small as 25 ml of peripheral blood while maintaining cell viability and compatibility with downstream characterization. MAR measurement is a promising approach for directly assaying single-cell therapeutic responses and for identifying cellular subpopulations with phenotypic resistance in heterogeneous tumors.
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