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Frontiers in oncology
2022;12 1016894.

Radioresistance in rhabdomyosarcomas: Much more than a question of dose.

Simona Camero, Matteo Cassandri, Silvia Pomella, Luisa Milazzo, Francesca Vulcano, Antonella Porrazzo, Giovanni Barillari, Cinzia Marchese, Silvia Codenotti, Miriam Tomaciello, Rossella Rota, Alessandro Fanzani, Francesca Megiorni, Francesco Marampon
Author Information
  1. Simona Camero: Department of Maternal, Infantile and Urological Sciences, Sapienza University of Rome, Rome, Italy.
  2. Matteo Cassandri: Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.
  3. Silvia Pomella: Department of Oncohematology, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
  4. Luisa Milazzo: Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  5. Francesca Vulcano: Department of Oncology and Molecular Medicine, Istituto Superiore di Sanità, Rome, Italy.
  6. Antonella Porrazzo: Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.
  7. Giovanni Barillari: Department of Clinical Sciences and Translational Medicine, University of Rome Tor Vergata, Rome, Italy.
  8. Cinzia Marchese: Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy.
  9. Silvia Codenotti: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
  10. Miriam Tomaciello: Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.
  11. Rossella Rota: Department of Oncohematology, Bambino Gesù Children's Hospital, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Rome, Italy.
  12. Alessandro Fanzani: Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
  13. Francesca Megiorni: Department of Experimental Medicine, "Sapienza" University of Rome, Rome, Italy.
  14. Francesco Marampon: Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University of Rome, Rome, Italy.
PMID: 36248991 DOI: 10.3389/fonc.2022.1016894

Abstract

Management of rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children, frequently accounting the genitourinary tract is complex and requires a multimodal therapy. In particular, as a consequence of the advancement in dose conformity technology, radiation therapy (RT) has now become the standard therapeutic option for patients with RMS. In the clinical practice, dose and timing of RT are adjusted on the basis of patients' risk stratification to reduce late toxicity and side effects on normal tissues. However, despite the substantial improvement in cure rates, local failure and recurrence frequently occur. In this review, we summarize the general principles of the treatment of RMS, focusing on RT, and the main molecular pathways and specific proteins involved into radioresistance in RMS tumors. Specifically, we focused on DNA damage/repair, reactive oxygen species, cancer stem cells, and epigenetic modifications that have been reported in the context of RMS neoplasia in both and studies. The precise elucidation of the radioresistance-related molecular mechanisms is of pivotal importance to set up new more effective and tolerable combined therapeutic approaches that can radiosensitize cancer cells to finally ameliorate the overall survival of patients with RMS, especially for the most aggressive subtypes.

Keywords

radiation therapy radioresistance radiosensitizers radiotherapy rhabdomyosarcoma

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