α-麦拉胜肽激素（α-MSH）及其受体黑素皮质激素1受体（MC1R）已被提出作为黑色素瘤研究中潜在的抗癌策略靶点，因为它们在组织特异性表达和参与黑色素细胞稳态方面发挥作用。然而，它们在黑色素瘤的预防和治疗中的作用仍存在争议。虽然大量证据支持α-MSH在预防黑色素瘤发展中的作用，但一些临床前研究结果表明，α-MSH下游信号传导可能促进免疫逃逸和癌症对治疗的耐药性。此外，在转移性黑色素瘤中，MC1R和α-MSH的过表达水平远高于正常细胞。此外，目标治疗（例如，在BRAFV600E突变肿瘤中的BRAF抑制）已被证明能增强这种现象。综上所述，这些数据表明，靶向MC1R可能作为治疗转移性黑色素瘤的一种手段。在本综述中，我们研究α-MSH的分子生物学特性，重点探讨其肿瘤相关性质，同时详述了关于α-MSH/MC1R轴与黑色素瘤和抗肿瘤策略之间的实验证据。© 2023. BioMed Central Ltd., part of Springer Nature.

Alpha-melanocyte stimulating hormone (α-MSH) and its receptor, melanocortin 1 receptor (MC1R), have been proposed as potential target for anti-cancer strategies in melanoma research, due to their tissue specific expression and involvement in melanocyte homeostasis. However, their role in prevention and treatment of melanoma is still debated and controversial. Although a large body of evidence supports α-MSH in preventing melanoma development, some preclinical findings suggest that the α-MSH downstream signalling may promote immune escape and cancer resistance to therapy. Additionally, in metastatic melanoma both MC1R and α-MSH have been reported to be overexpressed at levels much higher than normal cells. Furthermore, targeted therapy (e.g. BRAF inhibition in BRAFV600E mutant tumours) has been shown to enhance this phenomenon. Collectively, these data suggest that targeting MC1R could serve as an approach in the treatment of metastatic melanoma. In this review, we explore the molecular biology of α-MSH with particular emphasis into its tumor-related properties, whilst elaborating the experimental evidence currently available regarding the interplay between α-MSH/MC1R axis, melanoma and antitumor strategies.© 2023. BioMed Central Ltd., part of Springer Nature.