Pediatric cancer therapy and skeletal muscle growth: An emerging role for satellite cell disruption

Improvements in pediatric cancer survival has increased the risk of long-term, treatment-related complications, including persistent skeletal muscle deficits. These impairments are often interpreted through mechanisms derived from adult models, which emphasize mitochondrial dysfunction and metabolic stress. However, pediatric cancer therapies are delivered during periods of active growth, when skeletal muscle expansion depends on satellite cell-mediated myonuclear accretion and establishment of the adult stem cell pool. In this Perspective, we propose that radiation and chemotherapy disrupt satellite cell-dependent processes during development, leading to impaired muscle growth and long-term functional deficits. Evidence from radiation models demonstrates reduced satellite cell abundance, impaired regeneration, and persistent structural abnormalities throughout pediatric development, while emerging chemotherapy data indicate alterations in myogenic regulatory programs and reduced satellite cell number, with limited overlap with adult responses. Together, these findings support a framework in which pediatric cancer therapies impair developmental muscle growth rather than solely inducing atrophy. Targeting satellite cells may represent a therapeutic strategy to restore muscle development and improve long-term outcomes in pediatric cancer survivors.