Functional drug susceptibility testing using single-cell mass predicts treatment outcome in patient-derived cancer neurosphere models - Sorbonne Université Access content directly
Journal Articles Cell Reports Year : 2021

Functional drug susceptibility testing using single-cell mass predicts treatment outcome in patient-derived cancer neurosphere models

Abstract

Functional precision medicine aims to match individual cancer patients to optimal treatment through ex vivo drug susceptibility testing on patient-derived cells. However, few functional diagnostic assays have been validated against patient outcomes at scale because of limitations of such assays. Here, we describe a high-throughput assay that detects subtle changes in the mass of individual drug-treated cancer cells as a surrogate biomarker for patient treatment response. To validate this approach, we determined ex vivo response to temozolomide in a retrospective cohort of 69 glioblastoma patient-derived neurosphere models with matched patient survival and genomics. Temozolomide-induced changes in cell mass distributions predict patient overall survival similarly to O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and may aid in predictions in gliomas with mismatch-repair variants of unknown significance, where MGMT is not predictive. Our findings suggest cell mass is a promising functional biomarker for cancers and drugs that lack genomic biomarkers.
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hal-04536889 , version 1 (08-04-2024)

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Attribution - NonCommercial - NoDerivatives

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Max A Stockslager, Seth Malinowski, Mehdi Touat, Jennifer C Yoon, Jack Geduldig, et al.. Functional drug susceptibility testing using single-cell mass predicts treatment outcome in patient-derived cancer neurosphere models. Cell Reports, 2021, 37 (1), pp.109788. ⟨10.1016/j.celrep.2021.109788⟩. ⟨hal-04536889⟩
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