Defining Pathways for Bone Destruction and Preservation in Cancer

A RON Kinase inhibitor reduces bone destruction (CTX marker) and increases bone repair (BSAP marker) in mice. Females (treated), Males (control).

Bone destruction occurs during aging and numerous diseases, such as 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 the bone microenvironment.

Welm and colleagues showed 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, they 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 as well as initial clinical trials.

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RON kinase: A target for treatment of cancer-induced bone destruction and osteoporosis. Andrade K, Fornetti J, Zhao L, Miller SC, Randall RL, Anderson N, Waltz SE, McHale M, Welm AL. Sci Transl Med. 2017 Jan;9(374). pii: eaai9338.