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: |
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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. |
Databáze: |
Directory of Open Access Journals |
Externí odkaz: |
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