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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Veröffentlicht in:Nature biotechnology Jg. 34; H. 11; S. 1161 - 1167
Hauptverfasser: 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
Format: Journal Article
Sprache:Englisch
Veröffentlicht: New York Nature Publishing Group US 01.11.2016
Nature Publishing Group
Schlagworte:
14/1
38
59
631/67/1059/2326
631/67/2329
631/80/83
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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
Online-Zugang:Volltext
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Beschreibung
Zusammenfassung: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.
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these authors contributed equally to this work
ISSN:1087-0156
1546-1696
DOI:10.1038/nbt.3697