Reducing MYC's transcriptional footprint unveils a good prognostic gene signature in melanoma
Zacarías-Fluck, Mariano F (Vall d'Hebron Institut d'Oncologia)
Massó Vallés, Daniel (Vall d'Hebron Institut d'Oncologia)
Giuntini, Fabio (Vall d'Hebron Institut d'Oncologia)
González-Larreategui, Íñigo (Vall d'Hebron Institut d'Oncologia)
Kaur, Jastrinjan (Vall d'Hebron Institut d'Oncologia)
Casacuberta-Serra, Sílvia (Vall d'Hebron Institut d'Oncologia)
Jauset, Toni (Vall d'Hebron Institut d'Oncologia)
Martínez-Martín, Sandra (Vall d'Hebron Institut d'Oncologia)
Martín-Fernández, Génesis (Vall d'Hebron Institut d'Oncologia)
Serrano del Pozo, Erika (Vall d'Hebron Institut d'Oncologia)
Foradada Felip, Laia (Vall d'Hebron Institut d'Oncologia)
Grueso, Judit (Vall d'Hebron Institut d'Oncologia)
Nonell, Lara (Vall d'Hebron Institut d'Oncologia)
Beaulieu, Marie-Eve (Vall d'Hebron Institut d'Oncologia)
Whitfield, Jonathan R. (Vall d'Hebron Institut d'Oncologia)
Soucek, Laura (Vall d'Hebron Institut d'Oncologia)
Universitat Autònoma de Barcelona

Date:	2023
Abstract:	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.
Grants:	Ministerio de Economía y Competitividad IJCI-2014-22403 Instituto de Salud Carlos III PI19/01277
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Melanoma ; MYC ; Omomyc ; Signature
Published in:	Genes & Development, Vol. 37 (april 2023) , p. 303-320, ISSN 1549-5477

DOI: 10.1101/gad.350078.122
PMID: 37024284

18 p, 8.9 MB

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