Melanoma is a highly aggressive skin cancer with survival rates varying significantly based on stage and genomic characteristics. While localized melanoma has favorable outcomes, metastatic melanoma is associated with poor prognosis and limited treatment options. Radiotherapy (RT), one of the most commonly used cancer treatments, is less effective in melanoma due to its intrinsic radioresistance. This review discusses the current knowledge about the biological mechanisms contributing to melanoma radioresistance, including the role of cancer stem cells (CSCs), DNA repair mechanisms, hypoxia, altered metabolism, and melanin production. It also examines preclinical and clinical studies on novel therapeutic approaches, such as targeting CSC pathways, inhibiting DNA repair, modulating hypoxia-induced metabolic shifts, and combining RT with immunotherapies or targeted therapies. Promising strategies, such as RT-induced immune responses and advanced RT techniques, show the potential to overcome resistance. However, melanoma’s heterogeneity and the limited clinical validation of these approaches remain significant challenges. Integrated therapeutic strategies targeting the multifaceted mechanisms of melanoma radioresistance are essential to improve treatment outcomes. Further clinical validation and personalized approaches are needed to address the heterogeneity of melanoma and enhance the efficacy of novel interventions.
黑色素瘤是一种高度侵袭性的皮肤癌，其生存率因分期和基因组特征差异显著。局限性黑色素瘤预后较好，而转移性黑色素瘤则预后不良且治疗选择有限。放射治疗作为最常用的癌症治疗手段之一，因黑色素瘤固有的放射抵抗性而疗效受限。本综述探讨了当前关于黑色素瘤放射抵抗的生物学机制，包括肿瘤干细胞的作用、DNA修复机制、缺氧环境、代谢改变及黑色素生成的影响。同时分析了针对肿瘤干细胞通路、抑制DNA修复、调节缺氧诱导的代谢转变以及放疗联合免疫疗法或靶向治疗等新型治疗策略的临床前与临床研究。放疗诱导的免疫反应及先进放疗技术等策略展现出克服放射抵抗的潜力，但黑色素瘤的异质性及这些方法临床验证的不足仍是重大挑战。针对黑色素瘤放射抵抗的多维机制制定综合治疗策略，对改善治疗效果至关重要。未来需通过进一步临床验证和个体化治疗方案，以应对黑色素瘤的异质性并提升新型干预措施的疗效。
Confronting Melanoma Radioresistance: Mechanisms and Therapeutic Strategies
肿瘤(癌症)患者之家