RT Journal Article
SR Electronic
T1 Dissection of the Process of Brain Metastasis Reveals Targets and Mechanisms for Molecular-based Intervention
JF Cancer Genomics - Proteomics
JO Cancer Genomics Proteomics
FD International Institute of Anticancer Research
SP 245
OP 258
VO 13
IS 4
A1 ULRICH H. WEIDLE
A1 FABIAN BIRZELE
A1 GWENDLYN KOLLMORGEN
A1 RÜDIGER RÜGER
YR 2016
UL http://cgp.iiarjournals.org/content/13/4/245.abstract
AB 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.