Personalized drug stratification using endoscopic samples to assess ex vivo gastric cancer tissue susceptibility to chemotherapy and immune checkpoint inhibitors.

Customizing drug treatments based on individual tumor susceptibility and patient-specific factors is a complex task, highlighting the need for better predictive models tailored to each patient. Preserving tumor architecture is one strategy to address the intricate interactions between stromal cells and tumor cell populations within a patient. In this study, we explored the feasibility of using pretherapeutic endoscopic tissue cultures from patients (ePDTCs) with gastric and esophagogastric junction cancers to assess individual drug susceptibility. We treated these endoscopic tissue slice cultures with 5-FU (1 µM), a modified FLOT regimen comprising 5-FU (10 µM), leucovorin (10 µM), oxaliplatin (20 µM), and docetaxel (0.1 µM), the active metabolite of irinotecan (SN38, at 1 µM and 10 µM) and the PD-1 inhibitor nivolumab (3 µg/ml). Analysis of the tumor tissue revealed stable adaptations to the culture environment, which were further enhanced by adding 2% autologous human serum to the culture media. Dose-dependent responses were observed with SN38 across all samples and individual susceptibility at low concentrations. Both 5-FU and the FLOT regimen as well as PD-1 inhibition, tested at bioavailable dosages, further demonstrated individualized responses in ePDTCs. This study shows that ePDTCs can effectively assess tissue susceptibility to drugs, warranting further investigation in larger cohorts to validate this model's potential alongside clinical treatments.