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Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate

Author(s)
Maire, Cecile L; Murakami, Mark A; Knoff, David S; Liu, Huiyun; Idbaih, Ahmed; Weinstock, David M; Ligon, Keith L; Stevens, Mark M.; Chou, Shijie Nigel; Kikuchi, Yuki; Kimmerling, Robert John; Calistri, Nicholas L; Cermak, Nathan; Olcum, Selim A.; Cordero, Nicolas; Manalis, Scott R; Haidar, Samer, S.M. Massachusetts Institute of Technology; Wen, P.; ... Show more Show less
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Abstract
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 μl 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.
Date issued
2016-10
URI
http://hdl.handle.net/1721.1/108662
Department
Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Microsystems Technology Laboratories; Koch Institute for Integrative Cancer Research at MIT
Journal
Nature Biotechnology
Publisher
Nature Publishing Group
Citation
Stevens, Mark M; Maire, Cecile L; Chou, Nigel; Murakami, Mark A; Knoff, David S; Kikuchi, Yuki; Kimmerling, Robert J, et al. “Drug Sensitivity of Single Cancer Cells Is Predicted by Changes in Mass Accumulation Rate.” Nature Biotechnology 34, no. 11 (October 2016): 1161–1167.
Version: Author's final manuscript
ISSN
1087-0156
1546-1696

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