The molecular pathobiology of metastasis to the brain: a review

As the length of survival continues to improve for patients with systemic cancers, the problem of metastases to the chemotherapeutic sanctuary of the central nervous system (CNS) continues to grow. This review focuses on the pathobiology of brain metastasis, attempting to develop a framework for understanding the steps and molecular underpinnings of the metastatic cascade. In this process, cancer cells escape the primary tumor organ, intravasate into blood vessels, survive the hematogenous dissemination to the CNS, arrest in brain capillaries, extravasate, proliferate, and develop angiogenic abilities to succeed as an established metastasis. Each of the steps of the metastatic cascade is dependent on distinct molecular pathways, the identification of which may be exploited in attempting to halt or slow the development of brain metastases.