title: Drug sensitivity of single cancer cells is predicted by changes in mass accumulation rate.
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.
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Mark M
authors.initials: MM
authors.lastname: Stevens
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Cecile L
authors.initials: CL
authors.lastname: Maire
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Nigel
authors.initials: N
authors.lastname: Chou
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Murakami
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Knoff
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Hitachi High-Technologies Corporation, Ibaraki-ken, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kikuchi
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kimmerling
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Huiyun
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Samer
authors.initials: S
authors.lastname: Haidar
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Calistri
authors.affiliation: Program in Computational and Systems Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: Cermak
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Selim
authors.identifier: http://orcid.org/0000-0002-6417-1007
authors.initials: S
authors.lastname: Olcum
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Nicolas A
authors.initials: NA
authors.lastname: Cordero
authors.affiliation: 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.|AP-HP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Service de Neurologie 2-Mazarin, Paris, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Idbaih
authors.affiliation: Center For Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute, Cambridge, Massachusetts, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Weinstock
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute, Cambridge, Massachusetts, USA.|Department of Pathology, Boston Children's Hospital, Boston, Massachusetts, USA.|Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
authors.forename: Keith L
authors.initials: KL
authors.lastname: Ligon
authors.affiliation: Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.|Department of Mechanical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Manalis
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor / Q000295:instrumentation* / Q000379:methods; D004867:Equipment Design; D019544:Equipment Failure Analysis; D006801:Humans; D056656:Lab-On-A-Chip Devices; D055617:Micro-Electrical-Mechanical Systems / Q000295:instrumentation* / Q000379:methods; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents