Dr. Jiayuh Lin and colleagues at Nationwide Children’s Hospital have developed a drug to target the most common cancerous bone tumor in children, osteosarcoma, using a version of the FDA-approved drug, Celebrex. With the help of a two-year, $200,000 grant from Alex’s Lemonade Stand Foundation for Childhood Cancer, the team will begin testing the drug using human and canine tumor cell lines.
Osteosarcoma is an aggressive bone tumor that usually develops during the period of rapid growth that occurs in adolescence. A signaling pathway known as the STAT3 pathway is common in osteosarcoma and is crucial to tumor formation and cancer progression. Few drugs are available that can inhibit STAT3 and be clinically relevant.
“One of the main barriers to developing a clinical drug to inhibit STAT3 is finding lead compounds that exhibit desirable drug properties,” said Dr. Lin, who is a principal investigator in the Center for Childhood Cancer at The Research Institute at Nationwide Children’s Hospital.
Dr. Lin’s team has developed a STAT3-selective inhibitor, 8A, by applying a novel discovery method to Celebrex, which is typically prescribed to relieve pain, tenderness, swelling and symptoms of inflammatory conditions like osteoarthritis. 8A is more potent and selective than Celebrex against STAT3 signaling in osteosarcoma cells.
The new funding will allow Dr. Lin’s team to develop two additional 8A analogs that would further increase STAT3 binding, while retaining the desirable drug properties of Celebrex.