Patients with multiple myeloma often develop bone lesions resulting in skeletal-related events (SREs), such as spinal cord compression, vertebral collapse, pathologic fractures and bone pain. Bone lesions are caused by increases in osteoclast formation and are treated using antiresorptive drugs such as denosumab. This drug is an antibody that combats RANKL, a critical regulator of osteoclast formation, however, its use suppresses the immune system and increases the risk of serious infections.

Xu Feng, Ph.D., a professor in the UAB Department of Pathology’s Division of Molecular and Cellular Pathology, is working to develop a better targeting strategy.

“We want to use small molecules to target RANK signaling pathways that are involved in osteoclastogenesis and multiple myeloma SREs, but not in the immune system function,” says Feng.

Feng’s group previously discovered two motifs that regulate osteoclast formation in vitro.

“We believe that specifically targeting these two RANK motifs has the potential to serve as effective and selective therapeutic targets for bone lesions in multiple myeloma.”

The R21 grant supporting this project is funded by the National Cancer Institute in the amount of $476,733. The project will run through November 2026. Ralph Sanderson, Ph.D., is a collaborator with Feng on this grant.

“Our long-term goal is to develop safe and effective small molecule drugs targeting the two RANK motifs for preventing bone lesions in multiple myeloma.”