Unsanctifying the sanctuary: challenges and opportunities with brain metastases
Shannon Puhalla1, William Elmquist1, David Freyer1
1Division of Hematology/Oncology, University of Pittsburgh, Pittsburgh, Pennsylvania (S.P.); Department of Pharmaceutics, University of Minnesota, Minneapolis, Minnesota (W.E.); Department of Hematology/Oncology, Children's Hospital Los Angeles, Los Angeles, California (D.F.); Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University, Baltimore, Maryland (L.K.); Department of Pharmaceutical Sciences, School of Pharmacy, Texas Tech University Health Sciences Center, Amarillo, Texas (C.A.); Department of Pharmaceutical Sciences, School of Pharmacy, West Virginia University and the Mary Babb Randolph Cancer Center, Morgantown, West Virginia (P.L.); Department of Neurological Surgery, The Ohio State University Medical Center, Columbus, Ohio (J.M.); Blood Brain-Barrier Program, Oregon Health & Science University, Portland, Oregon (L.M., E.N.); Dotter Radiology/Neuroradiology, Oregon Health & Science University, Portland, Oregon (G.N.); Brain Tumor and Neuro-Oncology Center, Cleveland Clinic Foundation, Cleveland, Ohio (D.P.); School of Pharmacy, Texas Tech University, Health Sciences Center, Amarillo, Texas (Q.S.); Department of Psychiatry, Oregon Health & Science University, Portland, Oregon (S.W.); Portland Veterans Affairs Medical Center, Portland, Oregon (E.N.).
Abstract:
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.
