Malignant melanoma is a tumor characterized by a very high level of heterogeneity, responsible for its malignant behavior and ability to escape from standard therapies. In this review we highlight the molecular and biological features of the subpopulation of cancer stem cells (CSCs), well known to be characterized by self-renewal properties, deeply involved in triggering the processes of tumor generation, metastasis, progression and drug resistance. From the molecular point of view, melanoma CSCs are identified and characterized by the expression of stemness markers, such as surface markers, ATP-binding cassette (ABC) transporters, embryonic stem cells and intracellular markers. These cells are endowed with different functional features. In particular, they play pivotal roles in the processes of tumor dissemination, epithelial-to-mesenchymal transition (EMT) and angiogenesis, mediated by specific intracellular signaling pathways; moreover, they are characterized by a unique metabolic reprogramming. As reported for other types of tumors, the CSCs subpopulation in melanoma is also characterized by a low immunogenic profile as well as by the ability to escape the immune system, through the expression of a negative modulation of T cell functions and the secretion of immunosuppressive factors. These biological features allow melanoma CSCs to escape standard treatments, thus being deeply involved in tumor relapse. Targeting the CSCs subpopulation is now considered an attractive treatment strategy; in particular, combination treatments, based on both CSCs-targeting and standard drugs, will likely increase the therapeutic options for melanoma patients. The characterization of CSCs in liquid biopsies from single patients will pave the way towards precision medicine.

恶性黑色素瘤是以高度异质性为特征的肿瘤，其恶性行为和逃避标准疗法的能力导致。在这篇综述中，我们重点介绍了癌症干细胞（CSCs）亚群的分子和生物学特征，众所周知，其具有自我更新特性，并深深地触发了肿瘤的产生，转移，发展和耐药性的触发过程。从分子角度看，黑色素瘤CSCs通过干性标记物的表达来鉴定和表征，这些标记物包括表面标记物，ATP结合盒（ABC）转运蛋白，胚胎干细胞和细胞内标记物。这些单元具有不同的功能特征。特别地，它们在肿瘤传播过程中起着关键作用，由特定的细胞内信号传导途径介导的上皮到间质转化（EMT）和血管生成；此外，它们的特征在于独特的代谢重编程。如针对其他类型肿瘤的报道，黑素瘤中的CSCs亚群还具有低免疫原性以及通过表达T细胞功能的负调节和免疫抑制因子的分泌而逃避免疫系统的特征。 。这些生物学特征使黑素瘤CSC逃脱了标准治疗，从而深入参与了肿瘤的复发。现在，针对CSCs亚群是一种有吸引力的治疗策略。特别是，基于靶向CSCs和标准药物的联合治疗可能会增加黑色素瘤患者的治疗选择。