Tumor latency and dormancy are obstacles to effective cancer treatment. In brain metastases, emergence of a lesion can occur at varying intervals from diagnosis and in some cases following successful treatment of the primary tumor. Genetic factors that drive brain metastases have been identified, such as those involved in cell adhesion, signaling, extravasation, and metabolism. From this wealth of knowledge, vexing questions still remain; why is there a difference in strategy to facilitate outgrowth and why is there a difference in latency? One missing link may be the role of tissue biophysics of the brain microenvironment in infiltrating cells. Here, I discuss the mechanical cues that may influence disseminated tumor cells in the brain, as a function of age and disease. I further discuss in vitro and in vivo preclinical models such as 3D culture systems and zebrafish to study the role of the mechanical environment in brain metastasis in an effort of providing novel targeted therapeutics.
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