Functional drug susceptibility testing based on biophysical measurements predicts patient outcome in glioblastoma patient-derived neurosphere models

Functional precision medicine aims to match each cancer patient to the most effective treatment by performing drug susceptibility testing on the patient’s tumor cells. Despite promising feasibility studies, functional drug susceptibility testing is not yet used in clinical oncology practice to make treatment decisions. Often, functional testing approaches have measured drug response using metabolic assays such as CellTiter-Glo, which measures ATP as a proxy for numbers of viable cells. As a complement to these existing metabolic drug response assays, we evaluated whether biophysical assays based on cell mass (the suspended microchannel resonator mass assay) or size as measured by microscopy (the IncuCyte assay) could be used as a readout for drug response. Using these biophysical assays, we profiled the temozolomide responses of a retrospective cohort of 70 glioblastoma patient-derived neurosphere models with matched clinical outcomes and found that both biophysical assays predicted patients’ overall survival with similar power to MGMT promoter methylation, the clinical gold standard biomarker for predicting temozolomide response in glioblastoma. These findings suggest that biophysical assays could be a useful complement to existing metabolic approaches as “universal biomarkers” to measure sensitivity or resistance to anti-cancer drugs with a wide variety of cytostatic or cytotoxic mechanisms.