肿瘤放射抗性形成机制及低剂量放射治疗协同新型增敏策略对肿瘤放射抗性抑制作用的研究进展OA
Research progress in formation mechanism of tumor radioresistance and inhibitory effect of low-dose radiotherapy combination with novel sensitization strategies on tumor radioresistance
低剂量放射治疗(LDRT)通常指单次剂量0.5~2.0 Gy或总剂量低于10.0 Gy的放射治疗方式,其在降低正常组织毒性的同时保留抗肿瘤效应,具有免疫调节、血管正常化和肿瘤微环境重塑等独特生物学效应.然而,肿瘤放射抗性严重制约了LDRT的临床疗效.肿瘤放射抗性的形成涉及多重机制,包括DNA损伤修复系统过度激活、细胞周期检查点失调、抗凋亡通路激活、肿瘤微环境重塑、活性氧稳态失衡和表观遗传学改变等.近年来,多种新型增敏策略被开发并用于协同LDRT抑制放射抗性,包括基于高原子序数纳米材料的放射治疗增敏、靶向谷胱甘肽系统的氧化应激调控、针对糖酵解关键酶的代谢重编程和联合免疫检查点抑制剂的免疫调控等,相关策略在LDRT中显示出特别的应用前景.本研究阐明肿瘤放射抗性形成的分子机制,重点综述了放射治疗增敏策略的应用和机制,并从剂量优化、安全性评估和技术创新3个维度分析了临床转化面临的挑战,旨在为放疗增敏策略的优化设计和临床应用提供理论依据.
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.
于洋;叶舍予;魏可新;王志成
北华大学附属医院放射科,吉林 吉林 132011||吉林大学公共卫生学院 国家卫健委放射生物学重点实验室 吉林 长春 130021川北医学院附属医院放射科,四川 南充 637504北华大学附属医院手外科,吉林 吉林 132011吉林大学公共卫生学院 国家卫健委放射生物学重点实验室 吉林 长春 130021
医药卫生
恶性肿瘤低剂量放射治疗放射抗性放射治疗增敏纳米材料免疫治疗协同治疗
Malignant tumorLow-dose radiotherapyRadioresistanceRadiosensitizationNanomaterialsImmunotherapyCombination therapy
《吉林大学学报(医学版)》 2026 (3)
872-880,9
吉林省科技厅科技发展计划项目(YDZJ202401200ZYTS)
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