Forsøksdyr: Development of new regimens in treatment of pancreatic cancer

Godkjenningsdato 17.09.2020

Godkjenningsperiode 17.09.2020-17.09.2023

Pancreatic cancer is one of the cancers with the highest degree of malignancy with about 4% of patients surviving more than 5 years after diagnosis. Only a minority (10-15%) of patients can undergo potentially curative surgical resection, because early pancreatic cancer often doesn't cause any signs or symptoms. The majority of patients are diagnosed with advanced-stage pancreatic cancer, either metastatic (50%) with a median survival of 3-5 months or locally advanced cancer (30%)(6-10 months survival). It should also be noticed that patients with early lung metastases often don't have any signs of symptoms.Pancreatic cancer appears to be the only cancer that has not seen any improvement in mortality figures for both men and women in Europe during the past 20 years. The purpose of this project is pre-clinical development of new regimens of drug re-purposing for treatment of pancreatic cancer.
A foundation of cancer research over the last 30 years has been the use of cancer cell lines or tissues that can be grown in mice or rats. In the present study, we will use syngeneic transplantable models which refers to a mouse cancer cell line that results in tumors in inbred animals of the same genetic background. Thus, the tumor microenvironment and the host are from the same species. The models include orthotopic (pancreatic) implantation of cancer cells (OCC), and spleen and tail vein injection of cancer cells (TCC). C57BL/6 mice will be used in both models. This project will use 140 mice in order to provide a proof-of-concept evidence for developing better treatments of pancreatic cancer.
OCC model mimics patients with pancreatic cancer at the early stage, and thus the level of distress is expected to be low during the experiment (usually within 2 weeks). TCC model mimics patients with lung metastases at the early stage without the primary tumor formation. Thus, the level of distress is also expected to be low during the experiment (usually with 2 weeks). The mice will be daily monitored regarding general appearance and behavior, including body weight. 3R will be taken as a principle and used based on previous data from both our own experiments and others to maximally adhere to NC3Rs programme. For instance, we will perform in vitro and in silico experiments prior to and in parallel with these in vivo experiments in order to further reduce the use of mice, refine and possible replace some of the experiments. We will also utilize the available data from our previous studies and online databases and follow the literature timely to maximally avoid duplicating experiments and research.