Dissection of the Process of Brain Metastasis Reveals Targets and Mechanisms for Molecular-based Intervention

Cancer Genomics - Proteomics

FABIAN BIRZELE²  GWENDLYN KOLLMORGEN¹  ULRICH H. WEIDLE¹  RÜDIGER RÜGER¹ 

[1] oche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germanyoche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germanyoche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany;oche Innovation Center, Basel, Switzerlandoche Innovation Center, Basel, Switzerlandoche Innovation Center, Basel, Switzerland

关键词: Angiogenesis;    astrocytes;    biomarkers for brain metastasis;    blood-brain-barrier;    brain parenchyma;    genetics of brain metastasis;    microglia;    neuromimicry;    transmigration;    review;   

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

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.

【 授权许可】

Unknown