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

Abstract

SUMMARYFunctional 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 (FUTC) for ex vivo drug response interrogation. Analysis of murine Kras mutant FUTCs demonstrated pharmacological and adaptive signaling profiles comparable to subtype-matched cultured cells. Applying FUTC profiling on non-small cell lung cancer patient samples, we generated robust drug response data in 18 of 19 cases, where the cells exhibited targeted drug sensitivities corresponding to their oncogenic drivers. In one of these cases, an EGFR mutant lung adenocarcinoma patient refractory to osimertinib, FUTC profiling was used to guide compassionate treatment. FUTC profiling identified selective sensitivity to disulfiram and the combination of carboplatin plus etoposide and the patient received substantial clinical benefit from the treatment with these agents. We conclude that FUTC profiling provides a robust, rapid, and actionable assessment of personalized cancer treatment options.

Development of an adenosquamous carcinoma histopathology-selective lung cancer graft model

“…To address methodological limitations in evaluation of cancer treatment approaches, we and others have developed and validated methods for NSCLC functional diagnostics, including conditionally reprogrammed cells (CRCs) (Liu et al, 2012), long-term 3D organoid culture (Kim et al, 2019, Sachs et al, 2019) and analysis of functional uncultured tumor cells (FUTCs) (Talwelkar et al, 2021). These ex vivo models can complement GEMMs in preclinical cancer research.…”