Rhabdomyosarcomas are oncogene addicted to the activation of AVIL

Significance Rhabdomyosarcoma (RMS) is a common pediatric soft-tissue cancer. There are two main subtypes driven by distinct mechanisms. Currently, there is no targeted therapy for the disease. We found an oncogene AVIL, whose activity is often abnormally up-regulated in RMS. Silencing the gene kills RMS cells and prevents tumor formation in animals; yet, normal control cells are indifferent to the interference. Mechanistically, AVIL activation turns on both oncogene pathways in RMS. These findings support that AVIL may be a good therapeutic target and that targeting AVIL may be a viable approach for both types of RMS.