Brain metastases: biology and the role of the brain microenvironment.

Metastatic lesions constitute the most frequently occurring malignancy in the brain, and their detection portends a grim prognosis. Efforts to treat these lesions have failed partly because the biologic processes that govern their development are poorly understood. In recent years, it has become evident that metastases occur as a result of a multistep process involving a rigorous natural selection of cells in the primary tumor that bear molecular and biologic characteristics permitting brain metastasis. In addition, recent studies have uncovered the importance of the brain microenvironment and its contribution to the metastatic process. The development of targeted therapies against brain metastases demands a better understanding of these molecular processes and the factors that influence them. This review examines the interplay between tumor cells and host brain tissue in the context of our current understanding of the role of various molecules involved in the metastatic process.