Role of the blood-brain barrier in metastatic disease of the central nervous system.

Systemic therapy is an important backbone in the multimodal treatment approach of brain metastases. However, the blood-brain barrier or, more correctly, the blood-tumor barrier, as the properties of tumor-associated vessels differ from the physiologic state, potentially limits the passage of systemic drugs. Indeed, several preclinical and clinical investigations showed that the distribution of drugs is very heterogeneous within a given brain metastasis, despite the contrast enhancement in magnetic resonance imaging. Brain metastases may show lower intratumoral concentrations of some drugs as compared to extracranial tumor sites, resulting in mixed responses. Therefore, a more profound understanding of the role of the blood-brain/blood-tumor barrier is needed to effectively formulate clinical trial approaches on systemic therapy options in patients with brain metastases.