Forsøksdyr: Treatment of brain metastases using WP1066

Godkjenningsdato 26.03.2018

1. Background
Brain metastasis is associated with extremely poor patient prognosis, and current treatments are not effective. In order to study cancer metastasis, more appropriate preclinical models are needed. We have established a unique human metastasis model for studying metastatic progression, where we inject human metastatic tumor cells into the left cardiac ventricle of immunodeficient mice. We have done a detailed characterisation of the blood-brain barrier (BBB) in the tumor model. We are currently sharing our model and knowledge with several other research groups (in UK, Germany, USA, The Netherlands).

We have an ongoing collaboration with a research group at MD Anderson Cancer Center (Houston, TX), who has developed a STAT3 inhibitor (WP1066). They have a patent on it, and the drug is currently being evauated in clinical trials, for other cancer types than brain metastasis.

We have preliminary in vitro data, showing a very good effect on melanoma brain metastasis cell lines in cell culture using WP1066, and we would now like to evaluate the effects in our in vivo models.

2. Aim of the research
The aim of this project is to bring our research into a phase 1 clinical trial on cancer metastasis patients. The current application thus describes a set of important experiments, in order to achieve this.

3. Expected harm to the animals
None. It is not a hazardous substance or mixture according to regulation (EC) No 1272/2008.

4. Expected benefit for science and society
If successful, we hope to achieve a new and better treatment of cancer patients with metastatic spread to the brain.

5. How many and kind of animals to be used
We plan to use up to a total of 48 nod/scid mice in our experiments.

6. How the demand on RRR is to be achieved
We need to use animal models in our research, as in vitro models do not reflect the 3d structural behavior and physiological conditions in animals, and these conditions are crucial for metastatic spread of cancers in patients. Therefore, we are of the opinion that in vitro experiments are not sufficient to obtain our aim, which is to bring new treatment into the clinic.