TY - JOUR T1 - Dissection of the Process of Brain Metastasis Reveals Targets and Mechanisms for Molecular-based Intervention JF - Cancer Genomics - Proteomics JO - Cancer Genomics Proteomics SP - 245 LP - 258 VL - 13 IS - 4 AU - ULRICH H. WEIDLE AU - FABIAN BIRZELE AU - GWENDLYN KOLLMORGEN AU - RÜDIGER RÜGER Y1 - 2016/07/01 UR - http://cgp.iiarjournals.org/content/13/4/245.abstract N2 - 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. ER -