Targeting Osteoclasts in Bone Metastasis

Bryant Darnay, Ph.D.
Assistant Professor
Experimental Therapeutics

Identifying the fundamental cellular, molecular and genetic mechanisms controlling cell growth and differentiation is essential for understanding the evolution of disease and cancer. Identification of these processes and the gene products that modulate differentiation and cellular growth may provide novel targets for molecular therapeutics for cancer intervention. 

Bone metastasis affects 80-90% of patients with advanced prostate cancer or breast cancer. The mechanism of bone metastasis is not well understood. RANKL has been identified as an essential regulator of the formation and activation of bone-destroying osteoclasts and playing a role in metastatic bone cancer. Bryant Darnay, Ph.D., along with other scientists at MD Anderson is investigating the manipulation of RANKL, its receptor (RANK) and the signaling machinery within the osteoclast to prevent bone loss caused by osteoporosis and malignant tumors in animal models.

By understanding the mechanisms by which RANK and RANKL mediate their effects on the bone resorbing cells, it may be possible to develop effective new therapeutic approaches to treat bone-related diseases. The work from Dr. Darnay’s laboratory has defined the signaling system by which osteoclasts are formed and mediate bone resorption. His research has defined novel mechanisms that relay the signals from the outside of the cell to cause osteoclast maturation. Recently, his laboratory has developed novel agents that block osteoclast differentiation and function of which one has been patented. Importantly, Dr. Darnay’s observations and his expertise in osteoclast biology along with other clinicians at MD Anderson will provide the basis for clinical evaluation of these new agents in bone metastasis.