[Encounter of cancer cells with bone. Development of bone metastasis-specific targeting therapy]

Bone, as well as liver and lungs, is one of the most preferential metastatic targets for solid cancers including breast, prostate, and lung cancers. Control of the bone metastasis is clinically important ; because they are frequently associated with bone pain and pathological fracture which greatly diminish the quality of life for patients. Interaction between cancer cells and microenvironment of metastatic site play an important role for establishment of cancer metastasis. The understanding of their mechanisms has been improved in recent years, and they will be new therapeutic strategies to cure the bone metastasis. Bisphosphonates has been clinically used for the bone metastasis. In addition, RANKL-RANK targeted drugs and cathepsin K inhibitors are also expected to be fruitful drugs for the bone metastasis. In this review paper, we summarize the molecular mechanism of these drugs, especially with regarding to the breast cancer bone metastasis. Furthermore, we touch upon the ubiquitin ligase CHIP which recently found as a master gene in the progression and metastasis of breast cancer.