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REVIEW article

Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 12 - 2024 | doi: 10.3389/fcell.2024.1521523
This article is part of the Research Topic New Strategies for Treating Fusion-Driven Sarcomas View all 5 articles

Myogenesis Gone Awry: The Role of Developmental Pathways in Rhabdomyosarcoma

Provisionally accepted
Annika L Gustafson Annika L Gustafson 1,2,3Adam D Durbin Adam D Durbin 4Kristin B Artinger Kristin B Artinger 5Heide L Ford Heide L Ford 1,2,3*
  • 1 Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, United States
  • 2 Molecular Biology Graduate Program, University of Colorado Anschutz Medical Campus, Aurora, United States
  • 3 Medical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, United States
  • 4 Division of Molecular Oncology, Department of Oncology, St Jude Children’s Research Hospital, Memphis, Tennessee, United States
  • 5 Department of Diagnostic and Biological Sciences, University of Minnesota School of Dentistry, Minneapolis, United States

The final, formatted version of the article will be published soon.

    Rhabdomyosarcoma is a soft-tissue sarcoma that occurs most frequently in pediatric patients and has poor survival rates in patients with recurrent or metastatic disease. There are two major subtypes of RMS: fusion-positive (FP-RMS) and fusion-negative (FN-RMS); with FP-RMS typically containing chromosomal translocations between the PAX3/7-FOXO1 loci. Regardless of subtype, RMS resembles embryonic skeletal muscle as it expresses the myogenic regulatory factors (MRFs), MYOD1 and MYOG. During normal myogenesis, these developmental transcription factors (TFs) orchestrate the formation of terminally differentiated, striated, and multinucleated skeletal muscle. However, in RMS these TFs become dysregulated such that they enable the sustained properties of malignancy. In FP-RMS, the PAX3/7-FOXO1 chromosomal translocation results in restructured chromatin, altering the binding of many MRFs and driving an oncogenic state. In FN-RMS, re-expression of MRFs, as well as other myogenic TFs, blocks terminal differentiation and holds cells in a proliferative, stemcell-like state. In this review, we delve into the myogenic transcriptional networks that are dysregulated in and contribute to RMS progression. Advances in understanding the mechanisms through which myogenesis becomes stalled in RMS will lead to new tumor-specific therapies that target these aberrantly expressed developmental transcriptional pathways.

    Keywords: Rhabdomyosarcoma, myogenesis, Developmental heterogeneity, transcription factor (TF), targeted therapeutic agents

    Received: 01 Nov 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Gustafson, Durbin, Artinger and Ford. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Heide L Ford, Department of Pharmacology, University of Colorado Anschutz Medical Campus, Aurora, United States

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.