Wilms Tumor Studies Offer New Insights

Connecting two previously unrelated insights about the formation of a pediatric kidney cancer (Wilms tumor), researchers at the University of Texas (UT) Southwestern Medical Center have uncovered the means by which the cancer continues to grow, providing potential targets for more effective treatments in the future. Wilms tumor is the most common cancer of the kidney in children. Typically, the disease is treated with surgery, radiation, and chemotherapy. This combination is effective for many patients but has numerous side effects, and a cure remains elusive for those with aggressive disease. This situation has driven investigators at UT Southwestern to look for more effective and less toxic ways to treat Wilms tumor. Previously, pediatric investigators from the nationally recognized Kidney Cancer Program at UT Southwestern's Harold C. Simmons Comprehensive Cancer Center identified a new molecular subset of Wilms tumors driven by recurrent mutations at "hot spot" residues in genes of the microRNA (miRNA) processing pathway (Rakheja et al., Nat Comm, 2014). A miRNA is a tiny RNA that influences the production of specific proteins in cells. Nevertheless, it was unclear exactly why impairment of miRNA function caused Wilms tumors. In follow-up studies, the researchers identified a previously unknown connection between the miRNA pathway and insulin-like growth factor 2 (IGF2), a secreted protein that drives organ growth and is known to play a critical role in Wilms tumor and other cancers. In related work, the UT Southwestern scientists also identified new, miRNA-independent mechanisms of IGF2 regulation in Wilms tumor. "Our previous discovery of miRNA processing mutations opened a window into this important class of Wilms tumors," said Dr. James Amatruda, Associate Professor of Pediatrics, Molecular Biology, and Internal Medicine.
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