使神圣之地不再神圣：脑转移瘤面临的挑战与机遇
Unsanctifying the sanctuary: challenges and opportunities with brain metastases.
作者信息
Puhalla Shannon, Elmquist William, Freyer David, Kleinberg Lawrence, Adkins Chris, Lockman Paul, McGregor John, Muldoon Leslie, Nesbit Gary, Peereboom David, Smith Quentin, Walker Sara, Neuwelt Edward
机构信息
Division 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.).
出版信息
Neuro Oncol. 2015 May;17(5):639-51. doi: 10.1093/neuonc/nov023.
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.
虽然靶向治疗，尤其是放射外科的应用拓宽了中枢神经系统转移瘤的治疗选择，但患者反应甚微，预后仍然很差。许多全身化疗药物无法穿透血脑屏障（BBB），这限制了它们的使用，并使脑转移瘤成为一个日益严峻的临床挑战。需要有合适的临床前模型来适当模拟转移过程、血脑屏障和血瘤屏障（BTB），以便更好地评估能够增强通过这些屏障的递送或穿透这些屏障的治疗方法，并了解治疗抵抗机制。不同实体瘤之间以及实体瘤亚型内部的异质性进一步增加了确定最合适的治疗方法以及实验室和临床研究方法的难度。这篇综述文章讨论了专注于预防和治疗中枢神经系统转移瘤的疗法，特别是关于血脑屏障的疗法，以及这些疗法带来的挑战和机遇。
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