Metastasis prevention: targeting causes and roots.

The spread of tumor cells from the primary focus, metastasis, is the main cause of cancer mortality. Therefore, anticancer therapy should be focused on the prevention of metastatic disease. Key targets can be conditions in the primary tumor that are favorable for the appearance of metastatic cells and the first steps of the metastatic cascade. Here, we discuss different approaches for targeting metastasis causes (hypoxia, metabolism changes, and tumor microenvironment) and roots (angiogenesis, epithelial-mesenchymal transition, migration, and invasion). Also, we emphasize the challenges of the existing approaches for metastasis prevention and suggest opportunities to overcome them. In conclusion, we highlight the importance of clinical evaluation of the agents showing antimetastatic effects in vivo, especially in patients with early-stage cancers, the identification of metastatic seeds, and the development of therapeutics for their eradication.