Weil Robert J, Palmieri Diane C, Bronder Julie L, Stark Andreas M, Steeg Patricia S
Brain Tumor Institute, ND4-40 Lerner Research Institute, Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44195, USA.
Am J Pathol. 2005 Oct;167(4):913-20. doi: 10.1016/S0002-9440(10)61180-7.
Clinically symptomatic metastases to the central nervous system (CNS) occur in approximately 10 to 15% of patients with metastatic beast cancer. CNS metastases are traditionally viewed as a late complication of systemic disease, for which few effective treatment options exist. Recently, patients with Her-2-positive breast tumors who were treated with trastuzumab have been reported to develop CNS metastases at higher rates, often while responding favorably to treatment. The blood:brain barrier and the unique brain microenvironment are hypothesized to promote distinct molecular features in CNS metastases that may require tailored therapeutic approaches. New research approaches using cell lines that reliably and preferentially metastasize in vivo to the brain have been reported. Using such model systems, as well as in vitro analogs of blood-brain barrier penetration and tissue-based studies, new molecular leads into this disease are unfolding.
临床上有症状的中枢神经系统(CNS)转移发生在约10%至15%的转移性乳腺癌患者中。中枢神经系统转移传统上被视为全身性疾病的晚期并发症,对此几乎没有有效的治疗选择。最近,有报道称接受曲妥珠单抗治疗的Her-2阳性乳腺肿瘤患者发生中枢神经系统转移的几率更高,且往往在对治疗反应良好时出现。据推测,血脑屏障和独特的脑微环境会促进中枢神经系统转移中独特的分子特征,这可能需要量身定制的治疗方法。已报道了使用能在体内可靠且优先转移至脑部的细胞系的新研究方法。利用此类模型系统以及血脑屏障穿透的体外类似物和基于组织的研究,针对这种疾病的新分子线索正在不断涌现。