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Notch Signaling in Pediatric Soft Tissue Sarcoma

  • Cristina Cossetti
  • Alberto Gualtieri
  • Silvia Pomella
  • Elena Carcarino
  • Rossella RotaEmail author
Chapter

Abstract

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.

Keywords

Notch signaling Notch receptors Gamma-secretase Soft tissue sarcoma Rhabdomyosarcoma Ewing sarcoma Synovial sarcoma 

Abbreviations

DLL1, 3, 4

Delta-like 1, 3, 4

ES

Ewing sarcoma

GEMM

Genetically engineered mice models

GSI

Gamma secretase inhibitors

MAML1

Mastermind-like 1

NEC

Notch extracellular domain

NEXT

Notch extracellular truncation

NICD

Notch intracellular domain

NTM

Notch transmembrane domain

RMS

Rhabdomyosarcoma

SS

Synovial sarcoma

Notes

Acknowledgments

This work was financially supported by the Italian Association for Cancer Research (AIRC IG 15312).

Conflict of Interest/Disclosures

No conflict of interest

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Cristina Cossetti
    • 1
  • Alberto Gualtieri
    • 1
  • Silvia Pomella
    • 1
  • Elena Carcarino
    • 1
  • Rossella Rota
    • 1
    Email author
  1. 1.Laboratory of Angiogenesis, Department of OncohematologyOspedale Pediatrico Bambino GesùRomeItaly

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