Ron Kinase Inhibitor For Preventing And Treating Bone Loss

Methods of treating cancer-related osteoporosis by inhibiting RON kinase.

Over 70 percent of breast cancer patients develop bone metastases which can cause severe pain, nerve compression, hypercalcemia, and debilitating bone fractures. Development and growth of bone metastases depend on the interactions between cells in the bone-tumor microenvironment that increase survival and proliferation of tumor cells. Current treatment options for osteolytic bone metastasis are limited to bisphosphonates and expensive RANKL-blocking antibody therapy with many adverse side effects.

A new cost-effective treatment method utilizes a novel mechanism of action involving a RON kinase that activates macrophage-stimulating protein (MSP) which is a key driver of osteoclast activation in vivo. The pathway is independent of RANKL signaling. Inhibiting RON prevents both the development of osteolysis and the progression of existing osteolysis. Inhibiting this method also shows potential for treating bone loss due to osteoporosis.

Concept

• Reduces cost and side effects of osteolyltic bone metastasis and osteoporosis treatment.
• Prevents development and progression of osteolysis.
• Enables a novel mechanism for treating bone loss, independent of the RANKL-RANK pathway.
• Demonstrates potential as a combination therapy.

Andrade K, Fornetti J, Zhao L, et al (2017). RON kinase: a target for treatment of cancer-induced bone destruction and osteoporosis. Science Translational Medicine. 9(374): eaai9338. doi: 10.1126/scitranslmed.aai9338

Publication Number: US-2016-0367534-A1
Patent Title: Ron Inhibitors for Use in Preventing and Treating Bone Loss
Jurisdiction/Country: United States
Application Type: Non-Provisional

Lucia Irazabal
lu.irazabal@utah.edu