Please use this identifier to cite or link to this item: https://hdl.handle.net/11000/30784
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dc.contributor.authorRedondo-Muñoz, Marta-
dc.contributor.authorRodríguez Baena, Francisco Javier-
dc.contributor.authorAldaz, Paula-
dc.contributor.authorCaballé-Mestres, Adrià-
dc.contributor.authorMoncho-Amor, Verónica-
dc.contributor.authorOtaegi-Ugartemendia, Maddalen-
dc.contributor.authorCarrasco García, Estefanía-
dc.contributor.authorOlias Arjona, Ana-
dc.contributor.authorLasheras-Otero, Irene-
dc.contributor.authorSantamaria, Eva-
dc.contributor.authorBocanegra, Ana-
dc.contributor.authorChocarro, Luisa-
dc.contributor.authorGrier, Abby-
dc.contributor.authorDzieciatkowska M, Monika-
dc.contributor.authorBigas, Claudia-
dc.contributor.authorMartin, Josefina-
dc.contributor.authorUrdiroz-Urricelqui, Uxue-
dc.contributor.authorMarzo, Florencio-
dc.contributor.authorSANTAMARIA, ENRIQUE-
dc.contributor.authorKochan, Grazyna-
dc.contributor.authorEscors, David-
dc.contributor.authorLarrayoz, Ignacio M-
dc.contributor.authorHeyn, Holger-
dc.contributor.authorD’Alessandro, Angelo-
dc.contributor.authorStephan-Otto Attolini, Camille-
dc.contributor.authormatheu, ander-
dc.contributor.authorWellbrock, Claudia-
dc.contributor.authorAznar Benitah, Salvador-
dc.contributor.authorSanchez-Laorden, Berta-
dc.contributor.authorArozarena, Imanol-
dc.date.accessioned2024-01-26T22:18:23Z-
dc.date.available2024-01-26T22:18:23Z-
dc.date.created2023-08-10-
dc.identifier.citationNature Metabolism . 2023 Sep;5(9):1544-1562es_ES
dc.identifier.issn2522-5812-
dc.identifier.urihttps://hdl.handle.net/11000/30784-
dc.description.abstractResistance of melanoma to targeted therapy and immunotherapy is linked to metabolic rewiring. Here, we show that increased fatty acid oxidation (FAO) during prolonged BRAF inhibitor (BRAFi) treatment contributes to acquired therapy resistance in mice. Targeting FAO using the US Food and Drug Administration-approved and European Medicines Agency-approved anti-anginal drug ranolazine (RANO) delays tumour recurrence with acquired BRAFi resistance. Single-cell RNA-sequencing analysis reveals that RANO diminishes the abundance of the therapy-resistant NGFRhi neural crest stem cell subpopulation. Moreover, by rewiring the methionine salvage pathway, RANO enhances melanoma immunogenicity through increased antigen presentation and interferon signalling. Combination of RANO with anti-PD-L1 antibodies strongly improves survival by increasing antitumour immune responses. Altogether, we show that RANO increases the efficacy of targeted melanoma therapy through its effects on FAO and the methionine salvage pathway. Importantly, our study suggests that RANO could sensitize BRAFi-resistant tumours to immunotherapy. Since RANO has very mild side-effects, it might constitute a therapeutic option to improve the two main strategies currently used to treat metastatic melanoma.es_ES
dc.formatapplication/pdfes_ES
dc.format.extent33es_ES
dc.language.isoenges_ES
dc.publisherNature Portfolioes_ES
dc.rightsinfo:eu-repo/semantics/openAccesses_ES
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.titleMetabolic rewiring induced by ranolazine improves melanoma responses to targeted therapy and immunotherapyes_ES
dc.typeinfo:eu-repo/semantics/articlees_ES
dc.contributor.instituteInstitutos de la UMH::Instituto de Neurocienciases_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s42255-023-00861-4es_ES
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