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From the Laboratory of Dr. Rossella Rota – a chapter in the new book Targeting Notch in Cancer (pp 277-312)

Notch Signaling in Pediatric Soft Tissue Sarcoma

Etiology, biology, response to treatment, and outcome greatly differ between adult and childhood cancers. Soft tissue sarcoma encompasses a heterogeneous group of pediatric sarcomas characterized by a high capacity to invade neighboring tissues. Although in the last years the overall survival in childhood cancers has improved to over 70% for the nonmetastatic forms, subgroups of young patients with metastatic and aggressive disease still show a poor outcome. Moreover, survivors often suffer from long-term morbidity due to the effects of therapy. It is widely accepted that soft tissue sarcomas of childhood develop from mesenchymal progenitor cells affected by chromosomal aberrations and mutations in genetic and epigenetic pathways during development. Therefore, pathways driving tissue differentiation are particularly relevant. Among these, the Notch signaling pathway plays one of the major roles. Notch signaling is evolutionarily conserved among species, working as a cell-to-cell communication system strictly defining cell fate, stem cell renewal, and tissue homeostasis during embryo development and in postnatal life. In the present chapter, we describe recent insights on Notch deregulation in the most prominent pediatric soft tissue sarcomas: rhabdomyosarcomas, Ewing sarcomas, and synovial sarcomas. We also summarize the challenges and opportunities in inhibiting Notch signaling for the treatment of this group of tumors.