Brain tumours develop in up to 35% of all cancer patients and they are associated with short survival times of less than 1.5 years from diagnosis.
Brain tumours have different characteristics than tumours in other organs and they are often resistant to standard therapies. Moreover, tightness of the blood vessels in the brain hinders access of drugs. In line with this unmet need for effective therapies, our objectives are:
- to use a subpopulation of white blood cells, which can efficiently penetrate blood vessels in the brain, as Trojan horses for the delivery of drugs
- to identify molecular targets specific to brain tumours and perform their validation at the pre-clinical level. Our findings are expected to inform the development of improved clinical therapies for brain tumours, thereby benefiting cancer patients.
In addition, our findings will enhance the understanding of basic biology, thereby advancing the brain tumour research field. Part of this work is a continuation from our previous project license.
To model brain tumours, cancer cells are implanted directly into the brain or administered into blood circulation, from where they subsequently enter the brain tissue. The vast majority of mice undergoing this procedure show mild or no symptoms. A small proportion of mice (around 0.3%) may experience stroke after the surgery, requiring immediate termination of the experiment, or tumour growth-related symptoms at the end of experiment. Those may include under-grooming, under-activity, and in rare cases (around 0.3%) lethargy or disorientation.
All surgery procedures are performed under general anaesthesia and pain killers are administered to minimise surgery-related pain. Surgery techniques have been optimised such as to result in a very low percentage of mice experiencing adverse effects. Animals are closely monitored – including throughout the night whenever required – to warrant their wellbeing at all times. To reduce the number of mice used in these studies, tumour growth is monitored via specialised imaging technique in life animals and statistical approaches are used to calculate the minimal required numbers.
The development of approaches for improved delivery of drugs to brain tumours requires models in which the white blood cells travel from the bone marrow to the brain via blood vessels. This complex process requires a whole organism and can therefore only be recapitulated in live animals.
Moreover, characteristics of brain tissue that contribute to brain-specific growth of cancer cells can only be modelled in vivo, necessitating the use of animal models.
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