Fig. 3

Management of metastases to the CNS. At late progression stage, some cancers will metastasize to the CNS where microglia (innate immune cells) and tumor cells tightly interact. Due to their crucial function and localization in the brain, microglia are a key therapeutic target in the management of patients with metastases in the CNS. Several therapies have been developed (or are currently being investigated) to treat metastases to the CNS, including: 1) classical treatments that minimally improve patient survival and are not curative; 2) combination therapies that may have a significant impact on the disease outcome (e.g., increased survival) by controlling both tumor cells and its microenvironment (e.g., microglia); 3) some FDA-approved therapeutics (e.g., tamoxifen and pro-inflammatory cytokines) can re-establish the anti-tumor function of microglia by skewing their M2 phenotype; and 4) innovative therapies that are currently under development or tested: a prophylactic treatment with a TLR9 agonist, other molecules (e.g., TREM2, glatirameracetate, aingolimod, tissue plasminogen activator) that are effective in other diseases (e.g., multiple sclerosis, stroke), PET imaging using methionine and PBR28 tracers, and nanobiologics for drug delivery and specific microglia targeting