Abstract

To investigate the clinical applicability of the high throughput screening (HTS) using patient-derived tumor cells (PDC) which were established from patients with non-small cell lung cancer undergoing surgery. PDCs were isolated and cultured from surgical specimen from NSCLC at Samsung Medical Center. We performed the HTS for 24 drugs (23 targeted agents and 1 positive control drug) with a micropillar/microwell chip platform using PDCs. Scanned images of the live cells were obtained using an optical fluorescence. With 6 dosages per drug in 7 replicates, the dose response curves and corresponding IC50 values were calculated from the scanned images. From October 2015 to February 2016, 15 samples from patients with non-small cell lung cancer were collected. PDCs were successfully established in 12 (80%) patients, and nine of 12 cases were successfully cultured in 3-d suitable for 23-drug HTS platform. Three PDCs demonstrated a sensitivity to Neratinib (HER-2/EGFR inhibitor). These PDCs are currently being profiled to elucidate the underlying molecular mechanisms for neratinib sensitivity. Differential chemosensitivity were observed which suggests that this HTS platform based on 3D culture with micropillar/microwell chips and PDC model could potentially provide a preclinical tool for predicting the efficacy of targeted agents in lung cancer.

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