Sabău Adrian-Horațiu, Tinca Andreea-Cătălina, Niculescu Raluca, Cocuz Iuliu Gabriel, Cozac-Szöke Andreea Raluca, Lazar Bianca Andreea, Chiorean Diana Maria, Budin Corina Eugenia, Cotoi Ovidiu Simion
Doctoral School of Medicine and Pharmacy, University of Medicine, Pharmacy, Sciences and Technology "George Emil Palade" of Targu Mures, 540142 Targu Mures, Romania.
Pathophysiology Department, University of Medicine, Pharmacy, Sciences and Technology "George Emil Palade" of Targu Mures, 540142 Targu Mures, Romania.
Int J Mol Sci. 2025 Aug 1;26(15):7419. doi: 10.3390/ijms26157419.
Cutaneous malignant melanoma is an extraordinarily aggressive and heterogeneous cancer that contains a small subpopulation of tumor stem cells (CSCs) responsible for tumor initiation, metastasis, and recurrence. Identification and characterization of CSCs in melanoma is challenging due to tumor heterogeneity and the lack of specific markers (CD271, ABCB5, ALDH, Nanog) and the ability of cells to dynamically change their phenotype. Phenotype-maintaining signaling pathways (Wnt/β-catenin, Notch, Hedgehog, HIF-1) promote self-renewal, treatment resistance, and epithelial-mesenchymal transitions. Tumor plasticity reflects the ability of differentiated cells to acquire stem-like traits and phenotypic flexibility under stress conditions. The interaction of CSCs with the tumor microenvironment accelerates disease progression: they induce the formation of cancer-associated fibroblasts (CAFs) and neo-angiogenesis, extracellular matrix remodeling, and recruitment of immunosuppressive cells, facilitating immune evasion. Emerging therapeutic strategies include immunotherapy (immune checkpoint inhibitors), epigenetic inhibitors, and nanotechnologies (targeted nanoparticles) for delivery of chemotherapeutic agents. Understanding the role of CSCs and tumor plasticity paves the way for more effective innovative therapies against melanoma.
皮肤恶性黑色素瘤是一种极具侵袭性且异质性的癌症，其中一小部分肿瘤干细胞（CSCs）负责肿瘤的起始、转移和复发。由于肿瘤的异质性、缺乏特异性标志物（CD271、ABCB5、ALDH、Nanog）以及细胞动态改变其表型的能力，黑色素瘤中CSCs的鉴定和特征描述具有挑战性。维持表型的信号通路（Wnt/β-连环蛋白、Notch、Hedgehog、HIF-1）促进自我更新、治疗抗性以及上皮-间质转化。肿瘤可塑性反映了分化细胞在应激条件下获得干细胞样特征和表型灵活性的能力。CSCs与肿瘤微环境的相互作用加速疾病进展：它们诱导癌症相关成纤维细胞（CAFs）的形成和新血管生成、细胞外基质重塑以及免疫抑制细胞的募集，从而促进免疫逃逸。新兴的治疗策略包括免疫疗法（免疫检查点抑制剂）、表观遗传抑制剂以及用于递送化疗药物的纳米技术（靶向纳米颗粒）。了解CSCs和肿瘤可塑性的作用为针对黑色素瘤的更有效的创新疗法铺平了道路。
