Functional diagnostics using fresh uncultured lung tumor cells to guide personalized treatments

Functional profiling of a cancer patient’s tumor cells holds potential to tailor personalized cancer treatment. Here, we report the utility of fresh uncultured tumor-derived EpCAM+ epithelial cells (FUTCs) for ex vivo drug-response interrogation. Analysis of murine Kras mutant FUTCs demonstrates pharmacological and adaptive signaling profiles comparable to subtype-matched cultured cells. By applying FUTC profiling on non-small-cell lung cancer patient samples, we report robust drug-response data in 19 of 20 cases, with cells exhibiting targeted drug sensitivities corresponding to their oncogenic drivers. In one of these cases, an EGFR mutant lung adenocarcinoma patient refractory to osimertinib, FUTC profiling is used to guide compassionate treatment. FUTC profiling identifies selective sensitivity to disulfiram and the combination of carboplatin plus etoposide, and the patient receives substantial clinical benefit from treatment with these agents. We conclude that FUTC profiling provides a robust, rapid, and actionable assessment of personalized cancer treatment options. [Display omitted] Fresh uncultured tumor-derived epithelial cells (FUTCs) are amenable for drug testingProfiling of lung tumor and matched normal cells identifies cancer-selective treatmentsNSCLC FUTCs with targetable drivers expose genotype-matched responses or non-responsesThe FUTC approach can guide personalized therapy in compassionate patient care Point-of-care functional diagnostic tests are unavailable for lung cancer. Talwelkar et al. present a pharmacological assay that uses fresh uncultured tumor cells (FUTCs) to guide personalized therapy for lung cancer patients. Besides identifying genotype-matched drug sensitivities, FUTC profiling also predicts clinical non-responses and can be used to expose resistance mechanisms.