title: Dissection of the Process of Brain Metastasis Reveals Targets and Mechanisms for Molecular-based Intervention.
abstract: 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.
authors.affiliation: Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: Weidle
authors.affiliation: Roche Innovation Center, Basel, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Birzele
authors.affiliation: Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany.
authors.forename: Gwendlyn
authors.initials: G
authors.lastname: Kollmorgen
authors.affiliation: Roche Innovation Center Munich, Roche Diagnostics GmbH, Penzberg, Germany ruediger.rueger@roche.com.
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Rüger
mesh_terms: D000818:Animals; D015415:Biomarkers; D001812:Blood-Brain Barrier; D001932:Brain Neoplasms / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology*; D002450:Cell Communication; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D015398:Signal Transduction; D057705:Transendothelial and Transepithelial Migration; D059016:Tumor Microenvironment
chemical_list: D015415:Biomarkers
keywords: Angiogenesis; astrocytes; biomarkers for brain metastasis; blood-brain-barrier; brain parenchyma; genetics of brain metastasis; microglia; neuromimicry; review; transmigration