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Updated: Sep 25, 2025

Tumorsphere Derivation and Treatment from Primary Tumor Cells Isolated from Mouse Rhabdomyosarcomas
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The myogenesis program drives clonal selection and drug resistance in rhabdomyosarcoma

Anand G Patel1, Xiang Chen2, Xin Huang2

  • 1Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.

Developmental Cell
|April 28, 2022
PubMed

Insights

Pediatric rhabdomyosarcoma (RMS) recurrence is linked to chemotherapy-resistant cells. Targeting these cells, which resemble early muscle development, may prevent relapse in children with this cancer.

Area of Science:

  • Developmental Biology
  • Pediatric Oncology
  • Cancer Genomics

Background:

  • Rhabdomyosarcoma (RMS) is a pediatric cancer of skeletal muscle origin.
  • Unresectable or metastatic RMS presents poor prognoses due to high recurrence rates.

Purpose of the Study:

  • To investigate the cellular dynamics and developmental states within embryonal rhabdomyosarcoma (eRMS) tumors.
  • To identify therapeutic targets for preventing disease recurrence in eRMS.

Main Methods:

  • Single-cell and single-nucleus RNA sequencing of patient samples and patient-derived xenografts.
  • Analysis of tumor cellular hierarchy and developmental trajectories.
  • Assessment of EGFR signaling pathway dependency.

Main Results:

  • RMS tumors mimic the developmental spectrum of embryonal myogenesis.
  • Chemotherapy eradicates proliferative myoblasts, allowing expansion of immature paraxial mesoderm-like cells.
  • The paraxial mesoderm population is dependent on EGFR signaling and sensitive to EGFR inhibitors.

Conclusions:

  • Chemotherapy resistance in eRMS is driven by the expansion of immature, developmental-state cells.
  • Targeting EGFR signaling in these cells offers a potential strategy to prevent rhabdomyosarcoma recurrence.
  • A multi-targeted approach addressing each developmental state is crucial for improving eRMS outcomes.
Keywords:
cancer recurrencemuscle developmentsarcomasingle-cell biologytumor heterogeneity

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