Interfering with Hedgehog Pathway: New Avenues for Targeted Therapy in Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most frequent pediatric soft-tissue tumor accounting for about 7% of childhood malignancies. Multimodal therapy is the standard treatment for individuals with RMS but generally fails to cure high-risk group patients and can result in long-term side effects. Therefore, understanding the mechanisms driving RMS might help to find new candidate targets for more specific and effective therapeutic modalities. One of the molecular machineries which is often deregulated in cancer and specifically involved in tumorigenesis of RMS, is Hedgehog (Hh) signaling. There is increasing evidence that targeting this developmental pathway may hold promise in future treatment strategies for RMS. In this review, we discuss the contribution of the Hh pathway in RMS, the challenges of inhibiting this embryonic signaling in children with an update on recent preclinical data and ongoing clinical trials.