Abstract

Abstract Purpose: Liver metastases of pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease; most patients die within 5 years. There is a critical need to identify appropriate anticancer treatments for these patients. A patient-derived tumor xenograft (PDX) model in severe immunodeficient rat with primary PDAC xenografted into the liver is suitable for evaluating transcatheter hepatic arterial infusion chemotherapy. Materials and Methods: The purpose of this study was to develop a severe immunodeficient rat model with patient-derived primary PDAC xenografted into the liver, and to assess the treatment efficacy of hepatic arterial infusion chemotherapy with cisplatin in this model. Three patient-derived tumors of PDAC were transplanted into the liver of 21 rats each, totaling 63 rats. Four weeks after transplantation, the 21 rats were randomly assigned into three treatment groups of seven rats each: hepatic arterial infusion, systemic venous infusion, and control group. Tumor volumes were evaluated on CT twice at pre-treatment and 4-weeks post-treatment. Following euthanasia of the rats, resected tumor specimens were pathologically analyzed. Results: The liver-implanted PDAC PDX rat model was established in all 63 rats. hepatic arterial infusion chemotherapy and systemic venous infusion chemotherapy with cisplatin were able to be performed in the assigned rats. The hepatic arterial infusion group significantly inhibited tumor growth and reduced Ki67 expression, indicating lower cell proliferation, compared to the control group in three PDX tumors. Conclusion: A rat-based preclinical platform was established by liver-implanted PDAC PDX rat model. Arterial cisplatin infusion chemotherapy would be one of potential therapies for PDAC liver metastases. Citation Format: Ken Kageyama, Akira Yamamoto, Masanori Ozaki, Kenjiro Kimura, Shinpei Eguchi, Ryota Tanaka, Mizue Terai, Takami Sato, Yukio Miki. Treatment efficacy of transcatheter hepatic arterial infusion chemotherapy with cisplatin in a severe immunodeficient rat model with patient-derived primary pancreatic ductal adenocarcinoma xenografted into the liver [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6903.

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