Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate
Open Access
- 10 October 2016
- journal article
- research article
- Published by Springer Nature in Nature Biotechnology
- Vol. 34 (11) , 1161-1167
Abstract
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.Keywords
This publication has 31 references indexed in Scilit:
- Precision medicine for cancer with next-generation functional diagnosticsNature Reviews Cancer, 2015
- Patient-derived models of acquired resistance can identify effective drug combinations for cancerScience, 2014
- EGFR Variant Heterogeneity in Glioblastoma Resolved through Single-Nucleus SequencingCancer Discovery, 2014
- What a Tangled Web We Weave: Emerging Resistance Mechanisms to Inhibition of the Phosphoinositide 3-Kinase PathwayCancer Discovery, 2013
- Inconsistency in large pharmacogenomic studiesNature, 2013
- Circumventing Cancer Drug Resistance in the Era of Personalized MedicineCancer Discovery, 2012
- American Society of Clinical Oncology Clinical Practice Guideline Update on the Use of Chemotherapy Sensitivity and Resistance AssaysJournal of Clinical Oncology, 2011
- Tumour evolution inferred by single-cell sequencingNature, 2011
- Predicting drug susceptibility of non–small cell lung cancers based on genetic lesionsJournal of Clinical Investigation, 2009
- Molecular Determinants of the Response of Glioblastomas to EGFR Kinase InhibitorsNew England Journal of Medicine, 2005