Abstract 4616: Establishment of a metastatic orthotopic model of pancreatic ductal adenocarcinoma (PDAC) for drug development
Authors: Justyna Zdrojewska, Jenni H.E. Mäki-Jouppila, Jussi M. Halleen, Jenni Bernoulli
Journal: Cancer Research (2019)

Abstract Ductal adenocarcinoma of the pancreas (PDAC) has the worst survival prognosis (&amp;lt;5%) of all common gastrointestinal malignancies. PDAC is typically diagnosed at a very late stage when the tumor has already metastasized to other organs, at which point the treatment can no longer prolong the survival of the patients. To date, surgical resection is the only curative approach present, provided that the cancer is detected at a very early stage. Nonetheless, less than 20% of diagnosed patients qualify for the surgery and majority of these patients will eventually develop recurrence. Despite our advancing knowledge of the tumor biology of PDAC as well as recent improvements in diagnosis, the prognosis remains strikingly poor. The median survival observed after surgery followed by chemotherapy is about 20 months.The aim of this study was to establish an orthotopic model of PDAC that could be used to study efficacy of new potential treatments. Female athymic nude mice (Hsd: Athymic Nude-Foxn1nu) were used in this study. MiaPaCa-2-Luc human PDAC cells were injected to surgically exposed caudal part of the pancreas. At the time of inoculation, the animals were 4-5 weeks of age. To validate the model, the current standard-of-care (SOC) treatment (combination of nab-paclitaxel and gemcitabine) was used. During the study, tumor burden was quantified by imaging the bioluminescence signal emitted by the MiaPaCa-2-luc cells using IVIS Lumina II imaging system. After 30 days in study, tumor growth in the surgical area was observed. The mice were stratified to treatment groups based on similar intensity of the bioluminescent readout. Imaging was performed every second week after inoculation of the cells. The SOC treatment was initiated two weeks post inoculation and was administered twice a week over a period of 4-5 weeks. The observed tumor take rate was 100%. At sacrifice, tumor weight and volume were lower in the group receiving the SOC treatment as compared to the vehicle treated group. Although there were no differences in body weights, mice receiving the SOC treatment gained less weight when comparing the body weights obtained at endpoint relative to baseline. As confirmed by histological analyses at endpoint, the MiaPaCa-2-luc cells induced micrometastasis to other visceral organs including liver. In conclusion, a metastatic orthotopic PDAC model was established successfully and validated with the SOC treatment that slowed down disease progression. Therefore, this orthotopic model provides a promising tool for testing new treatments against PDAC in vivo. Citation Format: Justyna Zdrojewska, Jenni H.E. Mäki-Jouppila, Jussi M. Halleen, Jenni Bernoulli. Establishment of a metastatic orthotopic model of pancreatic ductal adenocarcinoma (PDAC) for drug development [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4616.