4.7 Article

Reducing MYC's transcriptional footprint unveils a good prognostic gene signature in melanoma

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GENES & DEVELOPMENT
卷 37, 期 7-8, 页码 303-320

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COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT
DOI: 10.1101/gad.350078.122

关键词

MYC; Omomyc; melanoma; signature

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In melanoma, inhibiting MYC with Omomyc leads to decreased tumor growth and metastatic capacity, and improves patient prognosis, highlighting the therapeutic potential of MYC inhibition in this disease.
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. In this study, Zacarias-Fluck et al. report the use of Omomyc, a MYC inhibitor, in targeting melanoma development, metastasis, and recurrence in human cell lines and CDX mouse models. By blocking MYC's transcriptional influence, Omomyc elicited gene expression signatures associated with good patient prognoses, pointing to the therapeutic potential of MYC inhibition in melanoma.

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