Department of Biology, University of Padua, 35131, Italy.
Department of Biology, University of Padua, 35131, Italy; Veneto Institute of Molecular Medicine (VIMM), Via Orus 2, 35129, Padua, Italy.
Redox Biol. 2020 Oct;37:101753. doi: 10.1016/j.redox.2020.101753. Epub 2020 Oct 8.
Cutaneous melanoma is the most aggressive type of skin cancer. Although cutaneous melanoma accounts for a minority of all types of skin cancer, it causes the greatest number of skin cancer related deaths worldwide. Oxidative stress and redox homeostasis have been shown to be involved at each stage of a malignant melanocyte transformation, called melanomagenesis, as well as during drug resistance. Reactive oxygen species (ROS) play an important and diverse role that regulate many aspects of skin cell behaviors ranging from proliferation and stemness, to oxidative damage and cell death. On the other hand, antioxidants are associated with melanoma spread and metastasis. Overall, the contribution of redox homeostasis to melanoma development and progression is controversial and highly complex. The aim of this study is to examine the association between redox homeostasis and the melanomagenic process. To this purpose we are presenting what is currently known about the role of ROS in melanoma initiation and progression. In addition, we are discussing the role of antioxidant mechanisms during the spread of the disease and in cases of melanoma drug resistance. Although challenging, targeting redox homeostasis in melanoma progression remains to be a promising therapeutic approach, especially valid during melanoma drug resistance.
皮肤黑色素瘤是最具侵袭性的皮肤癌类型。尽管皮肤黑色素瘤在所有皮肤癌类型中只占少数,但它却是全球导致皮肤癌相关死亡人数最多的癌症。氧化应激和氧化还原稳态已被证明参与了恶性黑素细胞转化的各个阶段,即黑色素瘤发生,以及耐药性的形成过程。活性氧(ROS)在调节皮肤细胞行为的许多方面发挥着重要且多样化的作用,范围从增殖和干性,到氧化损伤和细胞死亡。另一方面,抗氧化剂与黑色素瘤的扩散和转移有关。总的来说,氧化还原稳态对黑色素瘤发生和进展的贡献是有争议的,而且非常复杂。本研究的目的是研究氧化还原稳态与黑色素瘤发生过程之间的关联。为此,我们介绍了目前已知的 ROS 在黑色素瘤发生和进展中的作用。此外,我们还讨论了抗氧化机制在疾病传播和黑色素瘤耐药性中的作用。尽管具有挑战性,但针对黑色素瘤进展过程中的氧化还原稳态仍然是一种很有前途的治疗方法,尤其是在黑色素瘤耐药性期间。