Rapid and Sensitive Detection of Breast Cancer Cells in Patient Blood with Nuclease-Activated Probe Technology

Sven Kruspe; David D Dickey; Kevin T Urak; Giselle N Blanco; Matthew J Miller; Karen C Clark; Elliot Burghardt; Wade R Gutierrez; Sneha D Phadke; Sukriti Kamboj; Timothy Ginader; Brian J Smith; Sarah K Grimm; James Schappet; Howard Ozer; Alexandra Thomas; James O McNamara; Carlos H Chan; Paloma H Giangrande

doi:10.1016/j.omtn.2017.08.004

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Rapid and Sensitive Detection of Breast Cancer Cells in Patient Blood with Nuclease-Activated Probe Technology

Journal article

Open access

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Rapid and Sensitive Detection of Breast Cancer Cells in Patient Blood with Nuclease-Activated Probe Technology

Sven Kruspe, David D Dickey, Kevin T Urak, Giselle N Blanco, Matthew J Miller, Karen C Clark, Elliot Burghardt, Wade R Gutierrez, Sneha D Phadke, Sukriti Kamboj, …

Molecular therapy. Nucleic acids, Vol.8, pp.542-557

09/15/2017

DOI: 10.1016/j.omtn.2017.08.004

PMCID: PMC5577414

PMID: 28918054

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Abstract

A challenge for circulating tumor cell (CTC)-based diagnostics is the development of simple and inexpensive methods that reliably detect the diverse cells that make up CTCs. CTC-derived nucleases are one category of proteins that could be exploited to meet this challenge. Advantages of nucleases as CTC biomarkers include: (1) their elevated expression in many cancer cells, including cells implicated in metastasis that have undergone epithelial-to-mesenchymal transition; and (2) their enzymatic activity, which can be exploited for signal amplification in detection methods. Here, we describe a diagnostic assay based on quenched fluorescent nucleic acid probes that detect breast cancer CTCs via their nuclease activity. This assay exhibited robust performance in distinguishing breast cancer patients from healthy controls, and it is rapid, inexpensive, and easy to implement in most clinical labs. Given its broad applicability, this technology has the potential to have a substantive impact on the diagnosis and treatment of many cancers.

Breast Cancer

diagnostic nucleic acids

diagnostic markers

nucleases

cancer

circulating tumor cells

liquid biopsy

Details

Title: Subtitle: Rapid and Sensitive Detection of Breast Cancer Cells in Patient Blood with Nuclease-Activated Probe Technology
Creators: Sven Kruspe - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
David D Dickey - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Kevin T Urak - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Giselle N Blanco - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Matthew J Miller - Medical Scientist Training Program, University of Iowa, Iowa City, IA, USA
Karen C Clark - Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, IA, USA
Elliot Burghardt - Medical Scientist Training Program, University of Iowa, Iowa City, IA, USA
Wade R Gutierrez - Medical Scientist Training Program, University of Iowa, Iowa City, IA, USA
Sneha D Phadke - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Sukriti Kamboj - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Timothy Ginader - Department of Biostatistics, University of Iowa, Iowa City, IA, USA
Brian J Smith - Department of Biostatistics, University of Iowa, Iowa City, IA, USA
Sarah K Grimm - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA
James Schappet - Institute for Clinical and Translational Science, University of Iowa, Iowa City, IA, USA
Howard Ozer - Department of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA
Alexandra Thomas - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
James O McNamara - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Carlos H Chan - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, USA
Paloma H Giangrande - Department of Internal Medicine, University of Iowa, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Molecular therapy. Nucleic acids, Vol.8, pp.542-557
DOI: 10.1016/j.omtn.2017.08.004
PMID: 28918054
PMCID: PMC5577414
NLM abbreviation: Mol Ther Nucleic Acids
ISSN: 2162-2531
eISSN: 2162-2531
Publisher: Elsevier Inc
Grant note: name: DFG; name: NIH, award: T32 HL07344; name: NIH, award: R01CA138503, AI101391, AI106738; DOI: 10.13039/100000983, name: Mary Kay Foundation, award: 9033-12, 001-09; DOI: 10.13039/100001024, name: Roy J Carver Charitable Trust, award: RJCCT 01-224
Language: English
Date published: 09/15/2017
Academic Unit: Biostatistics; Surgery; Radiation Oncology; Mathematics; Holden Comprehensive Cancer Center; Internal Medicine
Record Identifier: 9983997492802771

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