Forsøksdyr: treatments combinations in cancer models

Godkjenningsdato 03.12.2020

Godkjenningsperiode 01.01.2021-31.12.2023

1 Purpose

This project will explore the possibility of treating cancer cell line-derived xenografts with a combination of radiation or PARP inhibitors, with inhibitors for other chromatin associated proteins . The aim is to propose clinical trials based on the results of these studies in order to improve standard of care for conditions such as oligometastatic primary prostate cancer, castration resistant prostate cancer, triple negative metastatic breast cancer, metastatic lung cancer, and metastatic melanoma.

2 Distress
Animals will be subcutaneously inoculated with human cancer cells and develop tumours. Tumours and body weight will be measured throughout the study, and animals will be restrained only during the measuring process. The tumours may grow fast and produce a morbid phenotype, which can cause distress to the animal. Some of the animals will be surgically castrated prior the beginning of the study, and there is a risk of infection associated with the surgery, as well as the secondary effects of hormone deprivation. The animals will be given inhibitors alone or in combination with focal radiation to the tumor, with doses adjusted to an acceptable level with minimal tolerable side-effects. Since some animals however might experience toxicity, the experiment will be classified as moderately influencing animal welfare.

3 Expected benefit
These experiments will allow to better position epigenetic therapy into the clinical landscape of several solid tumours management. Especially epigenetic treatment could be positions as adjuvant therapy for radiotherapy, e.g. if epigenetics treatment will radiosensitize metastases. Moreover in the management of prostate cancer patients, these studies will verify whether it is possible to reduce radiation doses, or use of the adjuvant treatment, and consequently to reduce the side effects derived from such treatments.

4 Number of animals, and what kind
We apply for the use of 2252 HSD: Athymic nude - Foxn1 nu (both male and female) over a period of four years.

5 How to adhere to 3R
In vitro experiments have shown informative and positive results, however it is required to confirm the observed patterns in vivo to determine the efficacy of the experimental treatments in pharmacological relevant doses in order to support clinical testing.
Number of animals is reduced by a prospective calculation of animals needed.
Animals will live in an enriched environment where they can play and run in a cardboard house and a running cylinder.Each animal will have daily follow up to detect behaviours associated with pain, and to measure weight and tumor sizes. Physical imprisonment or handling of the animals is only performed during weighing and measuring of the tumor sizes. Anaesthetic regimes are in place to reduce pain of tumor injections, and appropriate experimental endpoints for early intervention have been implemented.