Brain metastases, particularly from breast cancer, are a significant clinical problem. About one fifth of breast
cancer patients that develop metastatic disease will experience brain metastases. Survival is extremely poor, with a
median survival of approximately three months. One of the main issues with treating brain metastases is the late
stage at which the majority of brain metastases are diagnosed and the ineffectiveness of available therapies as a
consequence. At this late point, it is often too late for standard therapies to have a meaningful effect on the
progression of the tumours.
In recent years, the role of the immune system in the progression of systemic metastases has been described, with
circulating monocytes being found to play a significant role. However, little is known about the pathogenesis of
metastases within the brain. The brain possesses a very different environment to the rest of the body, with the blood
brain barrier (BBB) tightly regulating the movement of nutrients, drugs and cells into the brain. Consequently, the
processes that modeluate metastasis progression in other organs, such as lung and liver, may not be reflected within
the brain owing to its unique environment. The overall goal of this fellowship, therefore, will be to determine the
role of circulating monocytes in the development of brain metastases from breast cancer with the aim of identifying
potential therapeutic routes.
We believe that circulating monocytes may play a significant role in the development and progression of brain
metastases as a separate, distinct population from the resident macrophage population (microglia) within the brain.
We hypothesize that there is significant circulating monocyte infiltration into brain metastases, which is associated
with increased BBB breakdown and disease progression. On this basis, we propose that inhibiting these circulating
monocytes will significantly reduce both initiation and progression of brain metastasis.
Fields of science
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