Patient-derived esophageal adenocarcinoma organ chip: a physiologically relevant platform for functional precision oncology

Organ Model: Esophagus

Application: Cancer

Adapting a patient-centered approach, the authors leveraged a microfluidic cell culture technology platform, organoids derived from treatment-naive patient tumors or adjacent normal tissues, and patient-matched cancer-associated or normal fibroblasts respectively, to develop a novel, physiologically relevant, high-fidelity preclinical esophagus-on-a-chip model. H&E, immunofluorescence staining, live/dead assay, LDH assay, and ELISA-based detection of tumor biomarkers were used to assess treatment responses.

Each patient-specific stroma-inclusive microfluidic esophageal adenocarcinoma on-a-chip (EAC chip) faithfully recreates the tumor-stroma interface while preserving the full diversity of two cell types (epithelia and fibroblasts), genetic landscapes and histological architecture of the source tumors. EAC chips also accurately predict the response to neoadjuvant chemotherapy (NACT) within a clinically useful timeframe (approx. 12 days). A docetaxel-based triplet chemotherapy regimen matched with the treatment of the source patient was successfully perfused through the interstitial space within this model. Therefore, EAC chips more accurately recapitulate inpatient pathological and objective responses than the corresponding static 3D-organoid-only cultures.

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