The Role of Circulating Monocytes in the Development of Brain Metastases

ended

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.