Grant: Project Grant

BACKGROUND: Cancer can spread from its original site of origin, most commonly the lung, breast or skin, to the brain in a process called brain metastasis. Brain metastasis occurs in approximately 20% of patients with solid cancers and comes with a devastating prognosis. Our research has established two distinct types of brain metastases, one that exhibits extensive cancer cell invasion deep into the distant brain and another that is non-invasive and remains localized in one area of the brain. Our results show that patients with abundant invasion have poor outcomes compared to those with minimal invasion. The reasons why some brain metastases exhibit invasion and others do not remain unknown and is an important area of study. OBJECTIVES: The goal of this grant is to understand the underlying biology of cancer cell invasion into the brain. We will focus our efforts on: 1) identifying factors present in the cancer cells themselves that promote invasion, 2) understanding how reactive astrocytes, a specific type of brain cell that interacts with tumor cells, can enhance cancer cell invasion and 3) determine the nature of the immune microenvironment that surrounds minimally invasive versus highly invasive brain metastases. These approaches will uncover a number of mechanisms that may explain why some brain metastases exhibit invasion and others do not. SIGNIFICANCE: Understanding why some brain metastases are invasive, and others are not, has important implications for patients. We have already begun to use this information to guide changes to local treatment of brain metastases, such as surgery or radiation treatment. However, diving deeper into the underlying biology of this invasive process will allow us to find new drivers that might represent attractive targets for intervention. The long-term goals of this work are to generate knowledge that can be used to develop new therapeutic strategies for better clinical management of patients with brain metastases.