Preclinical models of cancer and metastases

Rationale

While treatment options for tumours that occur first in the body (primary tumours) are improving, cancer that has spread to other organs (metastases) is mostly incurable.

Cancer commonly spreads to several organs at the same time, requiring therapies that can simultaneously target metastases in multiple organs. 

Patients with brain cancer – with a primary tumour or metastatic cancer that has spread to the brain from other organs – have particularly poor prognosis. Our studies are therefore focusing on brain cancer and multi-organ metastases.

Plan of work and impact of our studies

To model primary tumours and metastases, cancer cells are implanted directly into the organ of origin or administered into blood circulation, from where they enter the metastatic organ. Our objectives are to investigate molecules involved in cancer cell growth and determine how our immune cells (white blood cells) attack tumours, and how this can be turned into therapies, such as exploiting white blood cells to deliver drugs to tumours.

Our findings are expected to inform the development of improved clinical therapies, benefiting cancer patients, as well as enhance the understanding of basic biology, advancing the metastases research field. Part of this work is a continuation from our previous project license.

Animal welfare 

Replacement

Characteristics of individual tissues that contribute to metastases-specific growth of cancer cells, proper maturation of white blood cells in the bone marrow, their activation in the lymph nodes and subsequent travel to tumours via the blood stream, all require a whole organism. As a result, these factors can only be modelled in a living organism, necessitating the use of mice.

Some aspects of our work have, however, been replaced by non-animal alternatives, such as culturing of cancer cells under different conditions and assays analysing the migration of white blood cells.

Reduction

To reduce the number of mice used in these studies, tumour growth is monitored using a specialist imaging technique for live animals, and statistical approaches are used to calculate the minimal required numbers.

Refinement

All surgery procedures are performed under general anaesthesia and pain killers are administered to minimise surgery-related pain. Surgery techniques have been optimised to result in a very low percentage of mice experiencing adverse effects. The vast majority of mice undergoing these procedures show mild or no symptoms.

A small proportion of mice (approximately 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 (less than 1.3%) lethargy or disorientation. The mice are closely monitored to warrant their wellbeing at all times.

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