MYC's key role in oncogenesis and tumor progression has long been established for most human cancers. In melanoma, its deregulated activity by amplification of 8q24 chromosome or by upstream signaling coming from activating mutations in the RAS/RAF/MAPK pathway—the most predominantly mutated pathway in this disease—turns MYC into not only a driver but also a facilitator of melanoma progression, with documented effects leading to an aggressive clinical course and resistance to targeted therapy. Here, by making use of Omomyc, the most characterized MYC inhibitor to date that has just successfully completed a phase I clinical trial, we show for the first time that MYC inhibition in melanoma induces remarkable transcriptional modulation, resulting in severely compromised tumor growth and a clear abrogation of metastatic capacity independently of the driver mutation. By reducing MYC's transcriptional footprint in melanoma, Omomyc elicits gene expression profiles remarkably similar to those of patients with good prognosis, underlining the therapeutic potential that such an approach could eventually have in the clinic in this dismal disease.

中文翻译：

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减少 MYC 的转录足迹揭示了黑色素瘤的良好预后基因特征

对于大多数人类癌症，MYC 在肿瘤发生和肿瘤进展中的关键作用早已得到证实。在黑色素瘤中，其通过扩增 8q24 染色体或来自激活 RAS/RAF/MAPK 通路突变的上游信号（该疾病中最主要的突变通路）的失调活性使 MYC 不仅成为黑色素瘤的驱动因子，而且成为黑色素瘤的促进因子进展，记录的影响导致积极的临床过程和对靶向治疗的抵抗。在这里，通过使用 Omomyc，迄今为止最具特征的 MYC 抑制剂，刚刚成功完成了 I 期临床试验，我们首次表明黑色素瘤中的 MYC 抑制诱导显着的转录调节，导致严重受损的肿瘤生长和独立于驱动突变的转移能力的明显消除。通过减少 MYC 在黑色素瘤中的转录足迹，Omomyc 引发的基因表达谱与预后良好的患者的基因表达谱非常相似，强调了这种方法最终可能在临床上治疗这种令人沮丧的疾病的潜力。