Single cell metabolic analysis to predict therapeutic response and identify targets for NSCLC

TECHNOLOGY: Diagnostic assays

High-throughput metabolic analysis of single tumor cells from liquid biopsy samples could be used to predict response to therapy and identify targets associated with drug resistance in NSCLC. The microscopy-based assay analyzes metabolic activity using fluorescent glycolysis and mitochondrial oxidation probes and allows tumor cell recovery for transcriptomic and genomic analyses to identify cellular targets associated with metabolic phenotypes. A computational model trained on assay data from malignant plural effusion samples from 32 lung adenocarcinoma patients, where elevated glycolysis relative to mitochondrial oxidation was associated with poor therapeutic response, predicted patient response to the therapies with an area under the curve (AUC) of 0.952. Single cell transcriptome sequencing of recovered cells linked elevated glycolysis to higher AXL receptor tyrosine kinase (AXL; UFO) expression, and the AXL inhibitor bemcentinib more potently killed patient cells with elevated glycolysis than those with elevated mitochondrial oxidation. ...