Overcoming the limits of pediatric brain tumor radiotherapy: The use of preclinical 3D models.

Fiche publication

Date publication

septembre 2024

Journal

Cancer radiotherapie : journal de la Societe francaise de radiotherapie oncologique

Auteurs

Membres identifiés du Cancéropôle Est :
Pr ENTZ-WERLE Natacha , Pr NOEL Georges , Dr BURCKEL Hélène , Dr CZUBA Elodie , Dr DESCHUYTER Marlène

Tous les auteurs :
Czuba E, Deschuyter M, Entz-Werlé N, Noël G, Burckel H

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/39327198

Résumé

Radiotherapy (RT) is an integral part of managing pediatric brain tumors, yet many patients develop tumor radioresistance, leading to recurrence and poor clinical outcomes. In addition, neurocognitive impairment is a common long-term side effect of RT, significantly impairing quality of life. Indeed, increasing evidence suggests that the developing child's brain is particularly vulnerable to the neurotoxic effects of ionizing radiation. Consequently, developing novel preclinical models is crucial for studying radiation's impact on normal brain tissue and predicting patient-specific responses to RT, enabling the development of personalized therapies combined with RT. However, this area remains underexplored, primarily due to the transfer of results gathered from in vitro tumor models from adults to pediatric entities while the location and molecular characteristics of the brain tumor differ. Recent years have seen the emergence of patient-specific 3D in vitro models, which have been established for entities including glioblastoma and medulloblastoma. These models better mimic primary parenteral tumors more closely in their histological, transcriptional, and mutational characteristics, thus approximating their intratumoral heterogeneity more accurately than conventional 2D-models. In this review, we presented the main limits of pediatric brain tumor radiotherapy, including mechanisms of radioresistance, associated tumor relapse, and the side effects of irradiation on the central nervous system. We also conducted an exhaustive review to identify studies utilizing basic or advanced 3D models of pediatric brain tumors combined with irradiation and discussed how these models can overcome the limitations of RT.