Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, United States.
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, United States.
Adv Cancer Res. 2024;162:125-143. doi: 10.1016/bs.acr.2024.06.002. Epub 2024 Jun 24.
Cases of melanoma are doubling every 12 years, and in stages III and IV, the disease is associated with high mortality rates concomitant with unresectable metastases and therapeutic drug resistance. Despite some advances in treatment success, there is a marked need to understand more about the pathology of the disease. The present review provides an overview of how melanoma cells use and modulate redox pathways to facilitate thiol homeostasis and melanin biosynthesis and describes plausible redox targets that may improve therapeutic approaches in managing malignant disease and metastasis. Melanotic melanoma has some unique characteristics. Making melanin requires a considerable dedication of cellular energy resources and utilizes glutathione and glutathione transferases in certain steps in the biosynthetic pathway. Melanin is an antioxidant but is also functionally important in hematopoiesis and influential in various aspects of host immune responses, giving it unique characteristics. Together with other redox traits that are specific to melanoma, a discussion of possible therapeutic approaches is also provided.
黑色素瘤的病例每 12 年就会翻一番,在 III 期和 IV 期,该疾病与无法切除的转移和治疗药物耐药相关,死亡率很高。尽管在治疗成功率方面取得了一些进展,但仍需要更多地了解疾病的病理学。本综述概述了黑色素瘤细胞如何利用和调节氧化还原途径来促进巯基稳态和黑色素生物合成,并描述了可能改善治疗恶性疾病和转移的合理氧化还原靶点。黑瘤性黑色素瘤具有一些独特的特征。产生黑色素需要大量的细胞能量资源,并在生物合成途径的某些步骤中利用谷胱甘肽和谷胱甘肽转移酶。黑色素是一种抗氧化剂,但在造血过程中也具有重要的功能,并在宿主免疫反应的各个方面产生影响,赋予其独特的特征。本文还讨论了可能的治疗方法,以及黑色素瘤特有的其他氧化还原特征。