Forsøksdyr: Bio-distribution and efficacy studies of metabolic anti-cancer drugs


Godkjenningsdato 13.04.2018

Breast cancer with an estimate of more than 500,000 deaths per year is the most common form of cancer in women. Biological markers, such as Estrogen Receptor, Progesterone Receptor and Human Epidermal Growth Factor Receptor 2, are currently used to sub-classify breast cancers to determine effective therapy. Individuals who test positive have a variety of treatment options. However, approximately 20% of all breast cancer patients test negative for all three markers and have a triple negative breast cancer phenotype. These patients have limited therapy options and hence a poor prognosis. In collaboration with Arctic Pharma we have developed a series of potential drugs that target the glycolytic pathway, which due to the Warburg effect is crucial for the growth of many cancer types, but not for the maintenance of healthy cells and tissues. Our drugs have been evaluated on various triple negative and luminal breast cancer cell lines. We have shown that they inhibit the proliferation (growth) of cancer cells and that they initiate cell death without affecting normal cells. Furthermore, we have, by analyzing lactate production and metabolic status of the treated cells, observed that our drugs specifically target the enzyme lactate dehydrogenase (LDH). LDH is the key factor of the glycolytic pathway and is crucial in cancer cells. We are now in the process of selecting the most promising drug candidates and are planning toxicity -and efficacy testing in mouse models.

In total, we will use 200 athymic nude foxn nu mice for the planned experiments. Drug concentrations lower than maximal tolerable dose (MTD) will be used for testing treatment effects and the harm for the animals is thus considered as moderate. The repeated oral gavage and handling also makes this a moderate experiment. For mice in the MTD experiment it will be betydelig belastende, but this will only be for a few animals and the animals will be sacrificed immitiatly when toxic effects are observed.

The 3R are taken into considerations by having evaluated the test substances in vitro before in vivo experiments are initiated, we will use as few mice as possible while it will still be possible to see differences between the treatments and for refinement the mice receives paper houses and paper so that they have something to play with..