Unsanctifying the sanctuary: Challenges and opportunities with brain metastases

Shannon Puhalla, William Elmquist, David Freyer, Lawrence Kleinberg, Chris Adkins, Paul Lockman, John McGregor, Leslie Muldoon, Gary Nesbit, David Peereboom, Quentin Smith, Sara Walker, Edward Neuwelt

Research output: Contribution to journalReview articlepeer-review

51 Scopus citations


While the use of targeted therapies, particularly radiosurgery, has broadened therapeutic options for CNS metastases, patients respond minimally and prognosis remains poor. The inability of many systemic chemotherapeutic agents to penetrate the blood-brain barrier (BBB) has limited their use and allowed brain metastases to become a burgeoning clinical challenge. Adequate preclinical models that appropriately mimic the metastatic process, the BBB, and blood-tumor barriers (BTB) are needed to better evaluate therapies that have the ability to enhance delivery through or penetrate into these barriers and to understand the mechanisms of resistance to therapy. The heterogeneity among and within different solid tumors and subtypes of solid tumors further adds to the difficulties in determining the most appropriate treatment approaches and methods of laboratory and clinical studies. This review article discusses therapies focused on prevention and treatment of CNS metastases, particularly regarding the BBB, and the challenges and opportunities these therapies present.

Original languageEnglish (US)
Pages (from-to)639-651
Number of pages13
Issue number5
StatePublished - May 1 2015

Bibliographical note

Publisher Copyright:
© 2015 The Author(s) 2015.


  • CNS sanctuary
  • brain metastases
  • imaging
  • prevention
  • therapy


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