Melanoma is the third most common type of skin cancer, characterized by its heterogeneity and propensity to metastasize to distant organs. Melanoma is a heterogeneous tumor, composed of genetically divergent subpopulations, including a small fraction of melanoma-initiating cancer stem-like cells (CSCs) and many non-cancer stem cells (non-CSCs). CSCs are characterized by their unique surface proteins associated with aberrant signaling pathways with a causal or consequential relationship with tumor progression, drug resistance, and recurrence. Melanomas also harbor significant alterations in functional genes (BRAF, CDKN2A, NRAS, TP53, and NF1). Of these, the most common are the BRAF and NRAS oncogenes, with 50% of melanomas demonstrating the BRAF mutation (BRAFV600E). While the successful targeting of BRAFV600Edoes improve overall survival, the long-term efficacy of available therapeutic options is limited due to adverse side effects and reduced clinical efficacy. Additionally, drug resistance develops rapidly via mechanisms involving fast feedback re-activation of MAPK signaling pathways. This article updates information relevant to the mechanisms of melanoma progression and resistance and particularly the mechanistic role of CSCs in melanoma progression, drug resistance, and recurrence.
黑色素瘤是第三常见的皮肤癌类型，其特点是异质性强且易向远处器官转移。该肿瘤由遗传特性各异的亚群构成，包含少量具有肿瘤起始能力的黑色素瘤干细胞样细胞及大量非干细胞样癌细胞。黑色素瘤干细胞通过独特的表面蛋白标志物及异常信号通路发挥作用，这些特征与肿瘤进展、耐药性及复发存在因果关联。黑色素瘤还存在功能基因（BRAF、CDKN2A、NRAS、TP53和NF1）的显著改变，其中BRAF与NRAS癌基因突变最为常见，约50%的黑色素瘤携带BRAFV600E突变。虽然靶向BRAFV600E治疗能改善患者总体生存率，但由于不良反应及临床疗效递减，现有治疗方案的长期效果有限。此外，通过MAPK信号通路的快速反馈再激活机制，耐药性会迅速产生。本文更新了黑色素瘤进展与耐药机制的相关信息，重点阐述了黑色素瘤干细胞在肿瘤进展、耐药及复发中的机制作用。
Mechanisms of Melanoma Progression and Treatment Resistance: Role of Cancer Stem-like Cells
肿瘤(癌症)患者之家