Hedgehog Signaling: A Therapeutic Target in Embryonal Rhabdomyosarcoma?

Rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, occurs in two major histological subtypes, embryonal (ERMS) and alveolar (ARMS). Aberrant Hedgehog (Hh) signalling due to germline mutations in the Hh receptor Patched (Ptch) has been linked to ERMS. Our goal is to better understand the role of this pathway in the pathogenesis of RMS, and to test it as a therapeutic target. Sixty per-cent of heterozygous Ptch mutant mice develop RMS resembling the human embryonal subtype. ERMS formation is accompanied by the silencing of the wild-type Ptch allele. Consistently, the formation of ERMS can be…