Abstract:

Low-dose radiotherapy （LDRT） generally refers to a radiotherapy modality with a single dose of 0.5-2.0 Gy or a total dose below 10.0 Gy. It reduces toxicity to normal tissues while retaining anti-tumor effects， and has unique biological effects such as immunomodulation， vascular normalization， and tumor microenvironment remodeling. However， tumor radioresistance severely restricts the clinical efficacy of LDRT. The development of tumor radioresistance involves multiple mechanisms， including overactivation of the DNA damage repair system， dysregulation of cell cycle checkpoints， activation of anti-apoptotic pathways， remodeling of the tumor microenvironment， imbalance of reactive oxygen species homeostasis， and epigenetic alterations. In recent years， various novel radiosensitization strategies have been developed to synergize with LDRT to inhibit radioresistance， including radiosensitization based on high-atomic-number nanomaterials， oxidative stress regulation targeting the glutathione system， metabolic reprogramming targeting key glycolytic enzymes， and immunomodulation combined with immune checkpoint inhibitors. These relevant strategies show particular application prospects in LDRT. This study elucidated the molecular mechanisms underlying tumor radioresistance， reviewed the applications and mechanisms of radiosensitization strategies， and analyzed the challenges in clinical translation from three dimensions： dose optimization， safety evaluation， and technological innovation， aiming to provide theoretical basis for the optimal design and clinical application of radiosensitization strategies.

Key words: Malignant tumor, Low-dose radiotherapy, Radioresistance, Radiosensitization, Nanomaterials, Immunotherapy, Combination therapy