Relative to adult cancers, pediatric cancers have a low mutational burden, if not mutations at all, with epigenetic deregulations playing key roles. They were indeed considered diseases of dysregulated development. In this scenario, pediatric Rhabdomyosarcoma, the most common soft tissue sarcoma of children and adolescents, represents a model of aberrant skeletal muscle differentiation.
In Rhabdomyosarcoma, myogenic transcription factors and related developmental pathways work in a deregulated way to modulate gene transcription in favor of a cancerous phenotype. Moreover, the Rhabdomyosarcoma subtype characterized by a chromosomal translocation t(2;13)(q35;q14) expresses a chimeric transcription factor, PAX3-FOXO1, which is the driver of the malignancy.
All these players have lost their pro-differentiation functions conversely affecting chromatin remodeling to initiate/sustain oncogenic circuitries.
The dissection of molecular pathways governing normal muscle tissue differentiation that are involved in Rhabdomyosarcoma opens the way to the identification of targeting strategies that can be applied to block tumor growth and/or sensitize tumor cells to conventional chemo- and radio-therapy. The goal is to find approaches that are more specific and less toxic for the young population affected by Rhabdomyosarcoma.
04/04/2025 Aula Ulrico Bracci (Policlinico Umberto I) ore 12. Dott. Rossella Rota Bambino Gesù Children's Hospital, Rome, Italy