New therapeutic targets for cancer bone metastasis

•We highlight newly identified molecular targets.•We discuss their molecular modes of action.•We summarize their preclinical and clinical validation.•We propose major goals and challenges for future investigation.

Bone metastases are dejected consequences of many types of tumors including breast, prostate, lung, kidney, and thyroid cancers. This complicated process begins with the successful tumor cell epithelial–mesenchymal transition, escape from the original site, and penetration into the circulation. The homing of tumor cells to the bone depends on both tumor-intrinsic traits and various molecules supplied by the bone metastatic niche. The colonization and growth of cancer cells in the osseous environment, which awaken their dormancy to form micro- and macro-metastasis, involve an intricate interaction between the circulating tumor cells and local bone cells including osteoclasts, osteoblasts, adipocytes, and macrophages. We discuss the most recent advances in the identification of new molecules and novel mechanisms during each step of bone metastasis that may serve as promising therapeutic targets.