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

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. [Display omitted] • In a retrospective study, ex vivo drug testing predicts GBM patient survival • Testing is based on detecting subtle changes in single-cell mass • Predictive power of functional testing is comparable to MGMT promoter methylation • Mass biomarker could be used in situations where genomic biomarkers are unavailable Stockslager et al. find in a retrospective study that functional drug susceptibility testing predicts the response of patients with glioblastoma to chemotherapy. By detecting subtle changes in tumor cell mass after ex vivo drug exposure, treatment response can be predicted with power comparable to the standard-of-care genomic biomarker. [ABSTRACT FROM AUTHOR]