Forsøksdyr: The link between obesity and cancer

Godkjenningsdato 31.08.2020

Godkjenningsperiode 01.10.2020-30.09.2024

1 Formål
To determine the molecular mechanism of obesity-induced breast and pancreatic cancers. Based on previous work we know that tumors that grow in obese mice activate a transcriptional program. Here we aim to tease out which the downstream genes are responsible for linking tumor initiation and obesity.

2 Skadevirkninger
Obesity in the mice will be induced by feeding the mice a high fat containing diet. This is considered harmless. Obese and non-obese mice will then have cancer cells implanted orthotopically. Tumor formation will then be followed close either by optical imaging or palpation. The overall readout of the experiment is tumor formation, meaning that the experiments will stop long before the tumor burden becomes hazardous.

3 Forventet nytteverdi
Obesity is estimated to be the cause of 15-20% of all cancer-related deaths. This places obesity second (after smoking) in preventable causes of cancer. Unfortunately, we do currently not understand how obesity links to cancer. This is particularly unfortunate since we, therefore, do not have the possibility of offering tailor-made treatment strategies for obese cancer patients. Currently, they receive the same treatment as non-obese cancer patients, although we do not have any rational reasons for this. The work presented herein aims to close this gap by identifying protein targets to prevent obesity-induced cancers.

4 Antall dyr og art
Antal: 1928. Art: Mus Musculus (C57BL/6J)

5 Hvordan etterleve 3R
Replace: Tumor growth and progression is a complex process, encompassing events such as invasive growth, angiogenesis, interaction with immune cells, and other members of the microenvironment. The use of traditional 2D and 3D in vitro assays do unfortunately not recapitulate all of these processes.
Reduce: We continuously aim at using the fewest possible mice for each experiment. The combined experience from our and other groups over the past 8 years have established that the minimum number of animals required to detect significant biological meaningful differences in tumor initiation studies is 6 mice per cohort.
Refine: The group has extensive experience in performing tumor implantation procedures, which ensure fast and reliable injections that inflict as little pain as possible for the mice. Here, both pre- and post-surgical analgesia will be used for pain relief.