Emerging insights into the molecular biology of brain metastases.

One of the foremost challenges in oncology is developing improved therapies for preventing and treating metastases to the brain. Recent research in this area is bringing about a shift in the understanding of brain metastases. Previously, the occurrence and poor outcomes associated with brain metastases have been largely attributed to the exclusion of anticancer drugs from the brain by the blood-brain barrier (BBB). However, studies in multiple tumor types have also demonstrated that brain metastases have significant molecular differences from primary tumors and extracranial metastases. These molecular differences may not only promote the formation of brain metastases, but they may also contribute to these tumors' poor responsiveness to therapies. Such changes may be intrinsic to the cancer cells or driven by unique interactions with the brain microenvironment. An improved understanding of the molecular characteristics of brain metastases that contribute to their aggressive behaviors will facilitate the development of rational, more effective treatments for these tumors.