Strategies for overcoming the blood–brain barrier for the treatment of brain metastases

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The era of targeted therapy for cancer has been punctuated by some resounding successes, but with few exceptions, metastases to the brain remain frustratingly difficult to treat. It is increasingly apparent that old concerns regarding the ability of therapeutic agents to penetrate the blood–brain barrier have not been brushed aside by high-affinity small-molecule kinase inhibitors and monoclonal antibodies. Indeed, illustrative trends, such as the increasing incidence of brain metastases from HER2+ breast cancer since the advent of trastuzumab therapy, have helped to solidify the concept of the CNS as a sanctuary site for cancer. With 200,000 patients diagnosed with brain metastases in the USA each year, the therapeutic challenge posed by the blood–brain barrier continues to be a big problem.

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