Improving CNS Delivery to Brain Metastases by Blood–Tumor Barrier Disruption

Brain metastases encompass nearly 80% of all intracranial tumors. A late stage diagnosis confers a poor prognosis, with patients typically surviving less than 2 years. Poor survival can be equated to limited effective treatment modalities. One reason for the failure rates is the presence of the blood–brain barrier (BBB) and blood–tumor barrier (BTB) that limit the access of potentially effective chemotherapeutics to metastatic lesions. Strategies to overcome these barriers include new small molecule entities capable of crossing into the brain parenchyma, novel formulations of existing chemotherapies, and disruptive techniques. Here, we review BBB physiology and BTB pathophysiology. Additionally, we review the limitations of routinely practiced therapies and three current methods being explored for BBB/BTB disruption for improved delivery of chemotherapy to brain tumors.