Cancer is one of the leading causes of death in women and men worldwide. The fatal outcome usually occurs after metastatic dissemination, and bone is by far the most common site of metastasis for breast and prostate cancer, the highest incidence neoplasia in women and men, respectively. However, while this is clear, the mechanisms through which the metastatic preference is established is not. An emerging concept in this regard is the premetastatic niche (PMN) establishment, i.e., the process through which tumors can influence the bone microenvironment from the primary site and make it permissive for their engraftment, before they migrate to the blood flow and metastasize. In this review, we discuss key microenvironmental players in the bone/bone marrow PMN, including osteoblasts, osteoclasts, and bone marrow adipocytes. We also describe the known PMNeducating factors, as well as the role of extracellular vesicles as emerging players in the bone/bone marrow PMN. An overview of current therapeutic developments aimed at targeting the bone PMN is also provided.
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