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Live Cell Mass Accumulation Measurement Non-Invasively Predicts Carboplatin Sensitivity in Triple-Negative Breast Cancer Patient-Derived Xenografts
journal contribution
posted on 2018-12-19, 09:13 authored by Graeme
F. Murray, Tia H. Turner, Kevin A. Leslie, Mohammad A. Alzubi, Daniel Guest, Sahib S. Sohal, Michael A. Teitell, J. Chuck Harrell, Jason ReedPrompt
and repeated assessments of tumor sensitivity to available
therapeutics could reduce patient morbidity and mortality by quickly
identifying therapeutic resistance and optimizing treatment regimens.
Analysis of changes in cancer cell biomass has shown promise in assessing
drug sensitivity and fulfilling these requirements. However, a major
limitation of previous studies in solid tumors, which comprise 90%
of cancers, is the use of cancer cell lines rather than freshly isolated
tumor material. As a result, existing biomass protocols are not obviously
extensible to real patient tumors owing to potential artifacts that
would be generated by the removal of cells from their microenvironment
and the deleterious effects of excision and purification. In this
present work, we show that simple excision of human triple-negative
breast cancer (TNBC) tumors growing in immunodeficient mouse, patient-derived
xenograft (PDX) models, followed by enzymatic disaggregation into
single cell suspension, is enabling for rapid and accurate biomass
accumulation-based predictions of in vivo sensitivity to the chemotherapeutic
drug carboplatin. We successfully correlate in vitro biomass results
with in vivo treatment results in three TNBC PDX models that have
differential sensitivity to this drug. With a maximum turnaround time
of 40 h from tumor excision to useable results and a fully-automated
analysis pipeline, the assay described here has significant potential
for translation to clinical practice.
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patient morbiditybiomass resultstriple-negative breast cancerLive Cell Mass Accumulation Measurement Non-Invasively Predicts Carboplatin SensitivityTriple-Negative Breast Cancer Patient-Derived Xenografts Prompttreatment regimenscancer cell biomasstumor sensitivityfully-automated analysis pipelinetumor materialimmunodeficient mousechemotherapeutic drug carboplatinvivo treatment results40 hbiomass protocolsdrug sensitivityturnaround timetumor excisioncell suspensionpatient-derived xenograftcancer cell linesvivo sensitivitybiomass accumulation-based predictionspatient tumorsTNBC PDX models
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