• Ivan Vičić and Borislav Belev.
• Ivan Vičić, Department of Oncology, University Hospital Center Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia, ivan.vicic1@gmail.com.
• Croat. Med. J. 2021 Jun 30; 62 (3): 270-282.

AbstractOwing to its frequent occurrence and severe clinical picture, bone metastasis is an important problem in the clinical course of tumor diseases. Bone metastasis develops when the physiological remodeling process is disrupted by tumor cells via the same molecular mechanisms used by native bone cells. The process includes molecular crosstalk between osteocytes and osteoblasts and osteoclasts. Osteolytic bone metastasis, most often seen in breast cancer, is characterized by promoted differentiation and function of osteoclasts and reduced osteoblast function. Tumor cells take advantage of factors released by bone tissue resorption, thus establishing a vicious cycle that promotes the metastatic process. In osteoblastic metastasis, most often seen in prostate cancer, osteoblast function and differentiation are promoted, while osteoclast activity is reduced, resulting in net gain of bone tissue. Mechanisms involved in the early stages of bone metastasis and cancer cell dormancy have been understudied, and their exploration may pave the way for potential therapeutic strategies. Tumor affects the bone marrow microenvironment via exosomes, soluble factors, and membrane-bound ligands. In this way, an initial lesion is established, which after a variable duration of disseminated tumor cells dormancy progresses to an overt condition. The current review deals with basic mechanisms involved in bone metastasis formation and propagation. We illustrated a disparity between the diversity and number of factors included in the disease pathophysiology and the number of available and developing therapeutic options. We also examined new therapeutic strategies affecting molecular pathways.

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