Functional drug susceptibility testing using single-cell mass predicts treatment outcome in patient-derived cancer neurosphere models
Name
PIIS221112472101247X.pdf
Description
Published version
Size
5.09 MB
Format
Adobe PDF
Checksum (MD5)
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Author(s)
Stockslager, Max A
Malinowski, Seth
Touat, Mehdi
Yoon, Jennifer C
Geduldig, Jack
Mirza, Mahnoor
Kim, Annette S
Wen, Patrick Y
Chow, Kin-Hoe
Ligon, Keith L
Date Issued
2021
Journal
Cell Reports
Publisher
Elsevier BV
Citation
Stockslager, Max A, Malinowski, Seth, Touat, Mehdi, Yoon, Jennifer C, Geduldig, Jack et al. 2021. "Functional drug susceptibility testing using single-cell mass predicts treatment outcome in patient-derived cancer neurosphere models." Cell Reports, 37 (1).
Version
Final published version
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.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CELREP.2021.109788
