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The Emerging Role and Clinical Significance of PI3K-Akt-mTOR in Rhabdomyosarcoma

Ilaria Versari1, Sara Salucci1, Alberto Bavelloni2

  • 1Department of Biomedical and NeuroMotor Sciences (DIBINEM), University of Bologna, 40126 Bologna, Italy.

Biomolecules
|March 28, 2025
PubMed

Insights

Rhabdomyosarcoma (RMS) is a pediatric cancer driven by the PI3K-Akt-mTOR pathway. Targeting this pathway offers new therapeutic strategies to improve survival rates for this aggressive disease.

Area of Science:

  • Pediatric Oncology
  • Molecular Biology
  • Cancer Therapeutics

Background:

  • Rhabdomyosarcoma (RMS) is a prevalent soft tissue sarcoma in children and young adults.
  • Embryonal RMS (eRMS) has a better prognosis than the aggressive alveolar RMS (aRMS).
  • Hyperactivation of the PI3K-Akt-mTOR pathway is common in RMS and linked to poor outcomes.

Purpose of the Study:

  • To review therapeutic strategies targeting the PI3K-Akt-mTOR pathway in Rhabdomyosarcoma.
  • To explore novel approaches for improving stagnant survival rates in RMS patients.
  • To highlight the pathway's critical role in RMS pathogenesis and treatment resistance.

Main Methods:

  • Literature review of therapeutic approaches targeting the PI3K-Akt-mTOR pathway.
  • Discussion of specific inhibitors (PI3K, Akt) and combination therapies.
  • Exploration of dietary supplements (curcumin) and repurposed drugs (chloroquine) for apoptosis induction.

Main Results:

  • The PI3K-Akt-mTOR pathway is a key driver of RMS cell proliferation, survival, and therapy resistance.
  • Targeted inhibitors and combination therapies show potential for enhancing treatment efficacy.
  • Dietary supplements and repurposed drugs may induce apoptosis in RMS cells.

Conclusions:

  • Targeting the PI3K-Akt-mTOR pathway is crucial for improving Rhabdomyosarcoma treatment.
  • Innovative strategies, including targeting super-enhancers and transcription factors, are needed.
  • Further research into targeted therapies holds promise for better patient outcomes in RMS.

Keywords:
AktPI3KmTORrhabdomyosarcoma

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