Strategies to Improve Sensitivity to Radiotherapy in Pediatric Solid Tumors

The primary goal in the treatment of pediatric malignancies is to maintain effective cancer control while minimizing toxicities and late effects. Radiotherapy is a component of standard therapy against many pediatric cancers, but tumor cell DNA damage repair mechanisms and the hypoxic tumor microenvironment may limit the effectiveness of this modality. Additionally, irradiated cancer cells often acquire resistance to radiotherapy that permits cancer cell survival or stimulates tumor regrowth after treatment, further limiting the efficacy of radiotherapy. Various preclinical studies have investigated the potential of combining chemotherapy or immunotherapy with radiotherapy, with the goal of inducing a more lethal amount of DNA damage and prohibiting cells from acquiring radiotherapy resistance. This review provides an overview of the current strategies to enhance cancer cell response to radiotherapy, providing a framework to improve outcomes for children with solid tumors.