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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\u00a0\u00b5M), a modified FLOT regimen comprising 5-FU (10\u00a0\u00b5M), leucovorin (10\u00a0\u00b5M), oxaliplatin (20\u00a0\u00b5M), and docetaxel (0.1\u00a0\u00b5M), the active metabolite of irinotecan (SN38, at 1\u00a0\u00b5M and 10\u00a0\u00b5M) and the PD-1 inhibitor nivolumab (3\u00a0\u00b5g\/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\u2019s potential alongside clinical treatments.<\/jats:p>","DOI":"10.1007\/s10238-025-01694-z","type":"journal-article","created":{"date-parts":[[2025,6,4]],"date-time":"2025-06-04T06:11:10Z","timestamp":1749017470000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Personalized drug stratification using endoscopic samples to assess ex vivo gastric cancer tissue susceptibility to chemotherapy and immune checkpoint inhibitors"],"prefix":"10.1007","volume":"25","author":[{"given":"Laura","family":"Hennig","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Astrid","family":"Monecke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngoc Anh","family":"Hoang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren\u00e9","family":"Thieme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian","family":"Prill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albrecht","family":"Hoffmeister","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Tuennemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingo","family":"Bechmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Lordick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonja","family":"Kallendrusch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,4]]},"reference":[{"key":"1694_CR1","first-page":"209","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, et al. 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Lordick received fees for lectures, expert appraisal or consulting services from Amgen GmbH, Astellas Pharma GmbH, AstraZeneca GmbH, Bayer AG, BioNTech SE, Bristol-Myers Squibb GmbH & Co. KGaA, Daiichi Sankyo Deutschland GmbH, Lilly Deutschland GmbH, Elsevier GmbH, Falk Foundation e.V., Incyte Inc, Merck KGaA, MSD Sharp & Dohme GmbH, Novartis Pharma GmbH, Roche Deutschland Holding GbmH, Servier Deutschland GmbH, Springe Nature AG & Co. KGaA, StreamedUp! GmbH; research projects are supported by Bristol-Myers Squibb GmbH und Co. KGaA and Gilead Science GmbH.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"188"}}