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

Autor: Max A. Stockslager, Seth Malinowski, Mehdi Touat, Jennifer C. Yoon, Jack Geduldig, Mahnoor Mirza, Annette S. Kim, Patrick Y. Wen, Kin-Hoe Chow, Keith L. Ligon, Scott R. Manalis
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cell Reports, Vol 37, Iss 1, Pp 109788- (2021)
Druh dokumentu: article
ISSN: 2211-1247
DOI: 10.1016/j.celrep.2021.109788
Popis: Summary: 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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