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

被引：78
作者：
Stevens, Mark M. [1 ,2 ]
Maire, Cecile L. [3 ]
Chou, Nigel [4 ]
Murakami, Mark A. [1 ,3 ]
Knoff, David S. [3 ]
Kikuchi, Yuki [5 ]
Kimmerling, Robert J. [1 ,4 ]
Liu, Huiyun [1 ,3 ]
Haidar, Samer [3 ]
Calistri, Nicholas L.
Cermak, Nathan [1 ,6 ]
Olcum, Selim
Cordero, Nicolas A. [1 ,3 ]
Idbaih, Ahmed [7 ,8 ]
Wen, Patrick Y. [9 ]
Weinstock, David M. [3 ,10 ]
Ligon, Keith L. [3 ,10 ,11 ,12 ]
Manalis, Scott R. [1 ,4 ,13 ]
机构：
[1] MIT, Koch Inst Integrat Canc Res, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[2] MIT, Dept Biol, Cambridge, MA USA
[3] Harvard Med Sch, Dept Med Oncol, Dana Farber Canc Inst, Boston, MA USA
[4] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[5] Hitachi High Technol Corp, Ibaraki, Japan
[6] MIT, Program Computat & Syst Biol, 77 Massachusetts Ave, Cambridge, MA 02139 USA
[7] UFMC Univ Paris 06, Sorbonne Univ, CNRS, UMR 7225,INSERM U 1127,UMR S 1127,ICM,Inst Cervea, Paris, France
[8] Hop Univ La Pitie Salpetriere Charles Foix, AP HP, Serv Neurol Mazarin 2, Faris, France
[9] Harvard Med Sch, Dana Farber Canc Inst, Ctr Neurooncol, Boston, MA USA
[10] Broad Inst, Cambridge, MA USA
[11] Boston Childrens Hosp, Dept Pathol, Boston, MA USA
[12] Brigham & Womens Hosp, Dept Pathol, 75 Francis St, Boston, MA 02115 USA
[13] MIT, Dept Mech Engn, Cambridge, MA 02139 USA
来源：
NATURE BIOTECHNOLOGY | 2016年 / 34卷 / 11期
基金：
美国国家卫生研究院;
关键词：
RESISTANCE; RECLASSIFICATION; GLIOBLASTOMA; CHEMOTHERAPY; MECHANISMS; MEDICINE; LEUKEMIA; GROWTH; SIZE;
D O I：
10.1038/nbt.3697
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
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.
引用
收藏
页码：1161 / +
页数：9
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