Finding a Novel Strategy Against Osteosarcoma

News Brief

Finding a Novel Strategy Against Osteosarcoma

Bone Cancer Illustration
Body

Osteosarcoma (OS) is the most common malignant childhood bone tumor. Most osteosarcoma deaths result not from the primary tumor but rather from metastatic disease. Decades of clinical trials have failed to improve the poor survival rates of patients with metastatic OS.

In research published online on January 9 in Molecular Cancer Therapeutics, David Loeb, M.D., Ph.D., and colleagues showed that DKK-1—a protein  found in bone, prostate, and other organs—is a promising target for OS therapy. DKK-1 is known to inhibit the Wnt signaling pathway, which has been implicated in osteosarcoma pathogenesis. The researchers found that a small-molecule inhibitor of DKK-1 activated Wnt signaling, causing reduced proliferation of OS cell lines and—in OS patient-derived mouse xenografts—inhibition of metastasis not by killing cancer cells but by causing them to differentiate into normal bone cells. The results justify developing therapies for OS metastasis that work by targeting DKK-1 or by manipulating Wnt signaling in other ways.

Dr. Loeb is professor of pediatrics and of developmental & molecular biology and the Linda and Earle Altman Faculty Scholar in Cancer Research at Einstein. He is also the chief of pediatric hematology/oncology at Einstein and Montefiore and a member of the National Cancer Institute-designated Montefiore Einstein Comprehensive Cancer Center.