• Jie Li, Huawei Xu, Lixing Zhang, Lele Song, Dan Feng, Xiaobo Peng, Meihong Wu, Yang Zou, Bin Wang, Lixing Zhan, Guoqiang Hua, and Xianbao Zhan.
• Department of Oncology, Changhai Hospital, Second Military Medical University, Shanghai, 200433, China.
• J. Cancer Res. Clin. Oncol. 2019 Nov 1; 145 (11): 2637-2647.

PurposeMalignant ascites (MA) is a common manifestation in advanced gastric cancer with peritoneal carcinomatosis and usually indicates a poor prognosis. However, lack of in vitro models that can faithfully recapitulate the characteristics of tumour cells in ascites hinders related researches. Tumour organoids have emerged as a robust in vitro model for tumour research and drug screening. Hence, we aimed to generate a 3-D in vitro organoid cultures from malignant ascites of gastric cancer for disease modelling and drug screening.MethodsEleven MADOs were generated from the MA tumour cells of gastric cancer patients. We made comparisons between MADOs and original MA tumour cells in histopathology by immunohistochemistry and genomics by whole-exome sequencing. In order to evaluate MADOs as functional in vitro disease models, we tested whether MADOs could be used for drug sensitivity screens.ResultsEleven MADO cultures from human gastric cancer were established. MADOs demonstrated divergent growth characteristics and morphologies. MADO cultures preserve the histological architecture, genomic landscape of the corresponding MA tumour cells. MADOs exhibited heterogeneous responses to standard-of-care chemotherapeutics.ConclusionsWe generated MADOs modelling characteristics and mutated genes of MA tumour cells. A broad range of intrinsic MADO response to conventional chemotherapeutics suggests MADOs are amenable to drug screening.

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