【佳学基因检测】Vemurafenib 耐药黑色素瘤细胞系的表征揭示了靶向治疗耐药的新特征

品牌基因检测联系方式—客观性

开题评估《肿瘤突变基因检测与个性化治疗方案的制定》《Int J Mol Sci》在. 2022 Aug 31;23(17):9910.发表了一篇题目为《Vemurafenib 耐药黑色素瘤细胞系的表征揭示了靶向治疗耐药的新特征》肿瘤靶向药物治疗基因检测临床研究文章。该研究由Martina Radić, Ignacija Vlašić, Maja Jazvinšćak Jembrek, Anđela Horvat, Ana Tadijan, Maja Sabol, Marko Dužević, Maja Herak Bosnar, Neda Slade 等完成。促进了肿瘤的精准治疗与个性化用药的发展，进一步强调了基因信息检测与分析的重要性。

肿瘤靶向药物及精准治疗临床研究内容关键词：

NME 转移抑制蛋白,耐药性,上皮间质转化（EMT）,黑色素瘤,信号通路,慢循环细胞,威罗非尼

肿瘤靶向治疗基因检测临床应用结果

尽管黑色素瘤的治疗有显着改善，但大多数患者会产生耐药性，其机制仍未完全了解。因此，我们生成并表征了两种黑色素瘤衍生细胞系，原发性 WM793B 和转移性 A375M，对 RAF 抑制剂威罗非尼具有获得性耐药性。耐药原发性 WM793B 黑色素瘤细胞的形态表现出 EMT 样特征，并表现出具有上皮和间充质特征的混合表型。令人惊讶的是，威罗菲尼耐药的黑色素瘤细胞表现出迁移能力下降，但也表现出集体迁移的趋势。信号通路分析揭示了 MAPK 的重新激活和 PI3K/AKT 通路的激活取决于威罗非尼耐药细胞系。对威罗非尼的获得性耐药导致原发性 WM793B 黑色素瘤细胞对化疗产生耐药性。此外，细胞周期分析和细胞周期调节剂水平的改变表明，抗性细胞可能会在 G0/G1 期短暂进入细胞周期停滞并获得慢周期细胞特征。在 WM793B 耐药的原发性黑色素瘤中发现 NME1 和 NME2 转移抑制蛋白水平降低，这可能是威罗非尼获得性耐药的结果，也是 PI3K/AKT 信号增加的原因之一。需要进一步的研究来揭示 NME 蛋白的威罗非尼依赖性负调节因子、它们在 PI3K/AKT 信号传导中的作用以及它们对威罗非尼耐药黑色素瘤细胞特征的影响。耐药性;上皮间质转化（EMT）；黑色素瘤;信号通路；慢循环细胞；威罗非尼。

肿瘤发生与复发转移国际数据库描述：

Regardless of the significant improvements in treatment of melanoma, the majority of patients develop resistance whose mechanisms are still not completely understood. Hence, we generated and characterized two melanoma-derived cell lines, primary WM793B and metastatic A375M, with acquired resistance to the RAF inhibitor vemurafenib. The morphology of the resistant primary WM793B melanoma cells showed EMT-like features and exhibited a hybrid phenotype with both epithelial and mesenchymal characteristics. Surprisingly, the vemurafenib-resistant melanoma cells showed a decreased migration ability but also displayed a tendency to collective migration. Signaling pathway analysis revealed the reactivation of MAPK and the activation of the PI3K/AKT pathway depending on the vemurafenib-resistant cell line. The acquired resistance to vemurafenib caused resistance to chemotherapy in primary WM793B melanoma cells. Furthermore, the cell-cycle analysis and altered levels of cell-cycle regulators revealed that resistant cells likely transiently enter into cell cycle arrest at the G0/G1 phase and gain slow-cycling cell features. A decreased level of NME1 and NME2 metastasis suppressor proteins were found in WM793B-resistant primary melanoma, which is possibly the result of vemurafenib-acquired resistance and is one of the causes of increased PI3K/AKT signaling. Further studies are needed to reveal the vemurafenib-dependent negative regulators of NME proteins, their role in PI3K/AKT signaling, and their influence on vemurafenib-resistant melanoma cell characteristics.Keywords: NME metastasis suppressor proteins; drug resistance; epithelial–mesenchymal transition (EMT); melanoma; signaling pathways; slow-cycling cells; vemurafenib.