Defining Pathways for Bone Destruction and Preservation in Cancer

Bone destruction occurs during aging and numerous diseases, including osteoporosis and cancer. Many cancer patients, including those with breast-to-bone metastasis, have bone osteolysis that is refractory to state-of-the-art treatments. Macrophage-stimulating protein (MSP) signaling, which is elevated in about 40% of breast cancers, promotes osteolytic bone metastasis by activation of the MSP signaling pathway in tumor cells or in the bone microenvironment. This work shows that MSP signals through its receptor, RON tyrosine kinase, which is expressed on the surface of host cells, to activate osteoclasts directly, by converging on the oncogene SRC. Thus, Welm and colleagues have identified RON tyrosine kinase as a viable target for reducing bone loss in patients who have breast-to-bone metastasis, and provided proof of this principle in mouse models and initial clinical trials.