Metastases to the central nervous system: Molecular basis and clinical considerations

Background: Metastatic tumors are the most common malignancies of the central nervous system (CNS) in adults. CNS metastases are associated with unfavorable prognosis, high morbidity and mortality. Lung cancer is the most common source of brain metastases, followed by breast cancer and melanoma. Rising incidence is primarily due to improvements in systemic control of primary malignancies, prolonged survival and advances in cancer detection. Purpose: To provide an overview of the metastatic cascade and the role of angiogenesis, neuroinflammation, metabolic adaptations, and clinical details about brain metastases from different primary tumors. Methods: A review of the literature on brain metastases was conducted, focusing on the pathophysiology and clinical aspects of the disease. PubMed was used to search for relevant articles published from January 1975 through December 2019 using the keywords brain metabolism, brain metastasis, metastatic cascade, molecular mechanisms, incidence, risk factors, and prognosis. 146 articles met the criteria and were included in this review. Discussion: Some primary tumors have a higher tendency to metastasize to the CNS. Establishing a suitable metastatic microenvironment is important in maintaining tumor cell growth and survival. Magnetic resonance imaging (MRI) is a widely used tool for diagnosis and treatment monitoring. Available treatments include surgery, radiotherapy, stereotactic radiosurgery, chemotherapy, immunotherapy, and systemic targeted therapies. Conclusions: Prevention of metastases to the CNS remains a difficult challenge. Advances in screening of highrisk patients and future development of novel treatments may improve patient outcomes.