Weidle Ulrich H, Birzele Fabian, Kollmorgen Gwendlyn, Rüger Rüdiger
Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany.
Roche Innovation Center, Basel, Switzerland.
Cancer Genomics Proteomics. 2016 Jul-Aug;13(4):245-58.
Brain metastases outnumber the incidence of brain tumors by a factor of ten. Patients with brain metastases have a dismal prognosis and current treatment modalities achieve only a modest clinical benefit. We discuss the process of brain metastasis with respect to mechanisms and involved targets to outline options for therapeutic intervention and focus on breast and lung cancer, as well as melanoma. We describe the process of penetration of the blood-brain-barrier (BBB) by disseminated tumor cells, establishment of a metastatic niche, colonization and outgrowth in the brain parenchyma. Furthermore, the role of angiogenesis in colonization of the brain parenchyma, interactions of extravasated tumor cells with microglia and astrocytes, as well as their propensity for neuromimicry, is discussed. We outline targets suitable for prevention of metastasis and summarize targets suitable for treatment of established brain metastases. Finally, we highlight the implications of findings revealing druggable mutations in brain metastases that cannot be identified in matching primary tumors.
脑转移瘤的发病率比原发性脑肿瘤高出十倍。脑转移瘤患者的预后很差，目前的治疗方式仅能带来有限的临床益处。我们从机制和相关靶点方面讨论脑转移过程，以概述治疗干预的选择，并重点关注乳腺癌、肺癌以及黑色素瘤。我们描述了播散的肿瘤细胞穿透血脑屏障（BBB）的过程、转移龛的建立、在脑实质中的定植和生长。此外，还讨论了血管生成在脑实质定植中的作用、外渗肿瘤细胞与小胶质细胞和星形胶质细胞的相互作用，以及它们的神经模仿倾向。我们概述了适合预防转移的靶点，并总结了适合治疗已形成脑转移瘤的靶点。最后，我们强调了在脑转移瘤中发现可靶向突变（而这些突变在匹配的原发性肿瘤中无法识别）所带来的影响。
