Tales of Cancer-Induced Bone Disease from the Senescent Osteocyte Crypt

Cancer-induced bone disease greatly diminishes the quality of life for patients with bone metastatic breast cancer, resulting in painful skeletal-related events including bone loss and fracture. Improved understanding of the roles of osteoblasts and osteoclasts, and how tumors alter their biology, has led to blockbuster therapies that significantly reduce skeletal-related events, but the disease remains incurable. However, emerging technologies and tools for studying the role of other stromal and immune components in controlling tumor-host interactions have begun to reveal new insights that may yield tractable therapeutic targets to further mitigate the painful effects of bone metastases. In this issue of Cancer Research, Kaur and colleagues study osteocytes, which are terminally differentiated osteoblasts and entombed within the bone matrix, from established bone metastatic breast cancer and report how the disease ages them as characterized by a senescence-associated secretory phenotype. This premature development of osteocyte senescence in turn enhances bone destruction and osteoclastogenic potential. Targeting senescent cells using senolytics suppressed bone resorption and preserved bone mass. Collectively, these findings underscore osteocyte involvement in the "vicious cycle" of bone metastasis, and targeting senescent osteocytes represents a new avenue for managing cancer-induced bone disease. See related article by Kaur et al., p. 3936.