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New Target for a Childhood Cancer

Using sequencing and other technologies, a team led by scientists from the St. Jude Children's Research Hospital have identified a new potential treatment target for alveolar rhabdomyosarcoma, an aggressive childhood soft tissue sarcoma. In a study appearing in this week's Science Translational Medicine, the researchers show that epigenetic histone alterations by a specific lysine demethylase, KDM4B, are required for the growth of a type of alveolar rhabdomyosarcoma characterized by the presence of the fusion protein Paired Box 3-Forkhead Box O1. Inhibition of KDM4 family members inhibited enhancer remodeling and, when combined with chemotherapy, led to reductions in tumor size in preclinical xenograft models. The findings, the authors write, "indicate that selectively inhibiting KDM4B by small molecules has translational potential in the context of a disease that is driven by a currently undruggable fusion oncoprotein.