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Nat Biotechnol. 2016 Nov;34(11):1161-1167. doi: 10.1038/nbt.3697. Epub 2016 Oct 10.

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

Author information

1
Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
2
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
3
Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
4
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
5
Hitachi High-Technologies Corporation, Ibaraki-ken, Japan.
6
Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
7
Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle épinière, ICM, Paris, France.
8
AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France.
9
Center For Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
10
Broad Institute, Cambridge, Massachusetts, USA.
11
Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA.
12
Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
13
Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

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.

PMID:
27723727
PMCID:
PMC5142231
DOI:
10.1038/nbt.3697
[Indexed for MEDLINE]
Free PMC Article

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