Forsøksdyr: Alternate Day Fasting and Cancer


Godkjenningsdato 23.11.2020

Godkjenningsperiode 04.01.2021-03.11.2025

1 Formål
To test how the metabolic environment created by alternate-day fasting affects tumor initiation. We have previously established how the obese environment significantly increases tumor initiation through epigenetic regulation of transcriptional programs (https://doi.org/10.1101/2020.08.11.244509
). Here we wish to test the opposite situation to gain further insights into the intricate relation between physiological homeostasis and cancer initiation.

2 Skadevirkninger
Alternate-day fasting has been performed in mice previously and this intervention does not change body weight, but rather increases insulin sensitivity compared to mice fed ad libitum. Overall, no adverse effects have been reported. Fasted and non-fasted 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
Metabolic reprogramming is a tumor hallmark. Tumor reliance of glucuse and glutamine has both been established and are both being used for diagnostics (PET scanning) and as therapeutic targets. However, our understanding of how the metabolism of the host affects tumor and in particular tumor formation is not well known. We hope that this pilot study will lead to further insights into tumor metabolism.

4 Antall dyr og art
These studies will be performed in wild-type C57BL6 mice. We ask to perform these pilot studies using two breast cancer models (E0771 and TeL) and two pancreas cancer models (C11 and KPC3601). Total number of mice: 96

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 does 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.