Osteosarcoma is the most common primary bone tumor of adolescents and young adults. Only 20% of patients with metastatic disease can now be cured. The Wnt signaling pathway drives normal osteoblast (bone-forming cell) differentiation, so researchers have speculated that aberrant Wnt signaling may cause osteosarcoma. The protein DKK-1 inhibits Wnt signaling and occurs at high levels in the blood of newly diagnosed osteosarcoma patients.

In research involving a mouse model of human osteosarcoma, David Loeb, M.D., Ph.D., has shown that an antibody that neutralizes DKK-1 increases Wnt signaling in the primary tumor and abolishes metastasis. Dr. Loeb received a five-year, $3.3 million NIH grant to test whether a small molecule inhibitor of DKK-1 affects Wnt signaling, tumor growth, and osteosarcoma metastasis in a mouse model.

Dr. Loeb is professor of pediatrics and of developmental and molecular biology at Einstein and chief of pediatric hematology/oncology at Einstein and Montefiore. (1R01CA262802-01)