Brain metastases are the most common cerebral tumor in adults currently affecting up to 30% of cancer patients. Advanced management of primary tumors has led to increased brain metastases incidence over the past years. Despite the severe clinical issue that is associated with brain metastases, current treatment options remain limited and standard of care therapy is mainly based on surgical resection, irradiation and chemotherapy. The failure of successful treatment of brain metastases can in part be attributed to the complex biology of the brain but also to the lack of insight into the cellular and molecular mechanisms that drive brain metastasis.
The brain represents a unique tissue environment with highly specialized brain-specific cells including astrocytes and microglia that execute important physiological functions such as maintenance of the blood-brain barrier and immune surveillance. Invasion of tumor cells disrupts the cellular homeostasis and leads to accumulation of brain-resident cells at metastatic lesions as well as recruitment of immune- and inflammatory cells from the periphery. Paracrine loops between tumor cells and tumor-associated stromal cells are known to critically affect disease progression and therapeutic response. However, our understanding how brain-metastatic cells from different primary tumors (melanoma, breast- and lung cancer) activate and exploit stromal cells to support rate-limiting steps of brain metastasis is currently limited.
Our research goal is to dissect cellular and molecular changes in the brain metastasis microenvironment in response to infiltrating tumor cells during different stages of metastatic colonization. We seek to understand how oncogene-driven signals convert intrinsically tumoricidal immune-and inflammatory cells into tumor-promoting cells during metastatic progression and in response to standard of care therapy.
Our long-term goal is to translate these findings into clinical applications for the development of targeted- or immune therapies that block tumor – stroma interactions or modulate tumor-associated inflammation in brain metastasis to provide better treatment options for brain metastases patients.