Brain Metastases · The Role of Circulating Monocytes in the Development of Brain Metastases

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