Lugović-Mihić Liborija, Ćesić Diana, Vuković Petra, Novak Bilić Gaby, Šitum Mirna, Špoljar Sanja
Professor Liborija Lugović-Mihić, MD, PhD, Department of Dermatovenerology , Sestre milosrdnice University Hospital Center, Vinogradska cesta 29, 10 000 Zagreb, Croatia;
Acta Dermatovenerol Croat. 2019 Sep;27(3):163-168.
The pathogenic features of melanomas include growth and amplification of atypical melanocytes associated with several features (self-sufficiency of growth factors, insensitivity to growth inhibitors, evasion of cellular apoptosis, limitless replicative potential, sustained angiogenesis, tissue invasion, and metastasis). These melanoma pathogenic events can be triggered by activating oncogenes or inactivating tumor-suppressor genes by means of molecular mechanisms such as dotted mutations, deletions, and translocations or epigenetic mechanisms such as microRNA expression and promoter methylation. In melanomas, an analysis of the gene aberrations in the genome has led to the discovery of the complex interaction of signaling pathways. Progression of melanomas also involves genetic instability and selective growth of cells with favorable mutations. Additional factors include genetic predisposition, mutagenesis, and suppressed host immune response. Some of the most important signaling pathways involved in the pathogenesis of melanoma are the MAPK, PI3K/PTEN/AKT, and MITF signaling pathways. Obtaining insight into the biology of melanocytes and pathogenesis of melanomas is important for the development of a targeted therapy (such as vemurafenib, dabrafenib, trametinib) as well as the immunotherapy (e.g. pembrolizumab, nivolumab, ipilimumab), which has enabled a substantial breakthrough in the treatment of patients with melanoma.
黑色素瘤的致病特征包括非典型黑素细胞的生长和扩增，与多种特征相关（生长因子的自给自足、对生长抑制剂不敏感、逃避细胞凋亡、无限复制潜能、持续血管生成、组织侵袭和转移）。这些黑色素瘤致病事件可通过分子机制（如点突变、缺失和易位）激活癌基因或使肿瘤抑制基因失活，或通过表观遗传机制（如微小RNA表达和启动子甲基化）引发。在黑色素瘤中，对基因组中基因畸变的分析已导致发现信号通路的复杂相互作用。黑色素瘤的进展还涉及遗传不稳定性和具有有利突变的细胞的选择性生长。其他因素包括遗传易感性、诱变和宿主免疫反应受抑制。黑色素瘤发病机制中一些最重要的信号通路是丝裂原活化蛋白激酶（MAPK）、磷脂酰肌醇-3激酶/磷酸酶和张力蛋白同源物/蛋白激酶B（PI3K/PTEN/AKT）以及小眼畸形相关转录因子（MITF）信号通路。深入了解黑素细胞生物学和黑色素瘤发病机制对于开发靶向治疗（如维莫非尼、达拉非尼、曲美替尼）以及免疫治疗（如帕博利珠单抗、纳武利尤单抗、伊匹木单抗）很重要，这些治疗已在黑色素瘤患者的治疗中取得了重大突破。
