College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada.
Int J Mol Sci. 2022 Aug 23;23(17):9520. doi: 10.3390/ijms23179520.
Nearly 100,000 individuals are expected to be diagnosed with melanoma in the United States in 2022. Treatment options for late-stage metastatic disease up until the 2010s were few and offered only slight improvement to the overall survival. The introduction of B-RAF inhibitors and anti-CTLA4 and anti-PD-1/PD-L1 immunotherapies into standard of care brought measurable increases in the overall survival across all stages of melanoma. Despite the improvement in the survival statistics, patients treated with targeted therapies and immunotherapies are subject to very serious side effects, the development of drug resistance, and the high costs of treatment. This leaves room for the development of novel approaches as well as for the exploration of novel combination therapies for the treatment of metastatic melanoma. One such approach is targeting melanin pigment with radionuclide therapy. Advances in melanin-targeting radionuclide therapy of melanoma can be viewed from two spheres: (1) radioimmunotherapy (RIT) and (2) radiolabeled small molecules. The investigation of mechanisms of the action and efficacy of targeting melanin in melanoma treatment by RIT points to the involvement of the immune system such as complement dependent cytotoxicity. The combination of RIT with immunotherapy presents synergistic killing in mouse melanoma models. The field of radiolabeled small molecules is focused on radioiodinated compounds that have the ability to cross the cellular membranes to access intracellular melanin and can be applied in both therapy and imaging as theranostics. Clinical applications of targeting melanin with radionuclide therapies have produced encouraging results and clinical work is on-going. Continued work on targeting melanin with radionuclide therapy as a monotherapy, or possibly in combination with standard of care agents, has the potential to strengthen the current treatment options for melanoma patients.
预计 2022 年美国将有近 10 万人被诊断患有黑色素瘤。直到 21 世纪 10 年代，晚期转移性疾病的治疗选择很少，只能略微提高总生存率。B-RAF 抑制剂和抗 CTLA4、抗 PD-1/PD-L1 免疫疗法被引入标准治疗方法，使所有阶段的黑色素瘤的总生存率都有了显著提高。尽管生存率统计数据有所改善，但接受靶向治疗和免疫疗法治疗的患者会出现非常严重的副作用、耐药性的发展，以及治疗费用高昂等问题。这为开发新方法以及探索治疗转移性黑色素瘤的新联合疗法留下了空间。一种这样的方法是用放射性核素疗法靶向黑色素。从两个方面可以看到黑色素瘤的黑色素靶向放射性核素疗法的进展：（1）放射性免疫疗法（RIT）和（2）放射性标记小分子。通过 RIT 靶向黑色素治疗黑色素瘤的作用机制和疗效的研究表明，免疫系统参与其中，如补体依赖性细胞毒性。RIT 与免疫疗法联合使用在小鼠黑色素瘤模型中表现出协同杀伤作用。放射性标记小分子领域专注于具有穿过细胞膜进入细胞内黑色素能力的放射性碘化合物，可用于治疗和成像作为治疗诊断学。用放射性核素疗法靶向黑色素的临床应用已产生令人鼓舞的结果，临床工作正在进行中。继续研究用放射性核素疗法作为单一疗法靶向黑色素，或可能与标准治疗药物联合使用，有可能增强黑色素瘤患者的现有治疗选择。
