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

The efficacy of cancer drugs is profiled by measuring changes in the mass of single tumor cells. 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...

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Vydáno v:	Nature biotechnology Ročník 34; číslo 11; s. 1161 - 1167
Hlavní autoři:	Stevens, Mark M, Maire, Cecile L, Chou, Nigel, Murakami, Mark A, Knoff, David S, Kikuchi, Yuki, Kimmerling, Robert J, Liu, Huiyun, Haidar, Samer, Calistri, Nicholas L, Cermak, Nathan, Olcum, Selim, Cordero, Nicolas A, Idbaih, Ahmed, Wen, Patrick Y, Weinstock, David M, Ligon, Keith L, Manalis, Scott R
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	New York Nature Publishing Group US 01.11.2016 Nature Publishing Group
Témata:	14/1 38 59 631/67/1059/2326 631/67/2329 631/80/83 64 64/60 Accumulation Agriculture Antineoplastic Agents - administration & dosage Bioassays Bioinformatics Biomedical Engineering/Biotechnology Biomedicine Biotechnology Cancer Cancer cells Cell Proliferation - drug effects Cells, Cultured Cellular biology Dose-Response Relationship, Drug Drug interactions Drug Resistance, Neoplasm Drug Screening Assays, Antitumor - instrumentation Drug Screening Assays, Antitumor - methods Equipment Design Equipment Failure Analysis Health aspects Heterogeneity Humans Lab-On-A-Chip Devices Leukemia Life Sciences Micro-Electrical-Mechanical Systems - instrumentation Micro-Electrical-Mechanical Systems - methods Neoplasms, Experimental - drug therapy Neoplasms, Experimental - pathology Neoplasms, Experimental - physiopathology Observations Pharmacology Subpopulations Treatment Outcome Tumors
ISSN:	1087-0156, 1546-1696
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Shrnutí:	The efficacy of cancer drugs is profiled by measuring changes in the mass of single tumor cells. 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.
Bibliografie:	SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 14 ObjectType-Article-1 ObjectType-Feature-2 content type line 23 these authors contributed equally to this work
ISSN:	1087-0156 1546-1696
DOI:	10.1038/nbt.3697