Rationale
Cancers of B-cells, a type of white blood cell that protects us against infections, often have an unfavourable prognosis and their treatment represents a major challenge for medicine.
In the UK, about 18,900 new cancers of B-cells were diagnosed in 2013, with about 7,700 reported deaths. In many of these cancers, particular 'factors' are abnormally active because of accidental genetic mutations. In normal B-cells, these factors control how much the cells grow. The uncontrolled activity of these factors due to genetic mutations promotes the uncontrolled growth of cells resulting in the formation of B-cell tumours, thus identifying the factors as potential drug targets.
Plan of work and impact of our studies
Here we propose to determine the functions of certain cancer-associated factors in normal and cancerous human B-cells, and to investigate how these factors contribute to the development of cancer. This project builds directly on our previous, published findings. The knowledge obtained from these studies is expected to help us better understand how certain cancers of B-cells arise by identifying the precise tumour-causing mechanisms underlying the cancer development. Importantly, our work will potentially establish new, more specific targets for drugs aimed at treating cancers of B-cells with abnormal activity of certain factors that have fewer side effects, paving the basis for personalised treatment of these devastating cancers.
Animal welfare
The biological reaction that generates the B-cells protecting us against infections, but that inherently bears the risk of developing cancers, is incredibly complex. It has been impossible to reproduce this reaction outside of the human body in a so called 'culture system', as the cells are fragile. Therefore, and particularly because the information gained from the experiments with animals is expected to be directly relevant for developing novel anti-cancer therapies against B-cell cancers, the use of animal models remains the only rational approach to study their role in the context of the complex living organism. Importantly, our previous extensive experience in animal research, documented by peer-reviewed publications, has allowed us to develop robust protocols involving the minimum numbers of animals required to provide reliable and informative results. Of exceptional importance for the planned studies is the fact that the B-cell system of mice is well characterized and closely resembles that of the human. For this reason, mice are most appropriate for an analysis of B-cells in health and disease. Mice will be monitored regularly and routinely for signs of ill health or distress throughout all aspects of the project.
Non-technical summary
Read in vivo function of proto-oncogenes in B-lymphocytes non-technical summary (PDF).
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