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Reprogramming miRNAs global expression orchestrates development of drug resistance in BRAF mutated melanoma

Drug resistance imposes severe limitations to the efficacy of targeted therapy in BRAF-mutated metastatic melanoma. Although this issue has been mitigated by the development of combination therapies with BRAF plus MEK inhibitors, drug resistance inevitably occurs with time and results in clinical re...

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Autores principales: Fattore, Luigi, Ruggiero, Ciro Francesco, Pisanu, Maria Elena, Liguoro, Domenico, Cerri, Andrea, Costantini, Susan, Capone, Francesca, Acunzo, Mario, Romano, Giulia, Nigita, Giovanni, Mallardo, Domenico, Ragone, Concetta, Carriero, Maria Vincenza, Budillon, Alfredo, Botti, Gerardo, Ascierto, Paolo Antonio, Mancini, Rita, Ciliberto, Gennaro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748102/
https://www.ncbi.nlm.nih.gov/pubmed/30254376
http://dx.doi.org/10.1038/s41418-018-0205-5
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author Fattore, Luigi
Ruggiero, Ciro Francesco
Pisanu, Maria Elena
Liguoro, Domenico
Cerri, Andrea
Costantini, Susan
Capone, Francesca
Acunzo, Mario
Romano, Giulia
Nigita, Giovanni
Mallardo, Domenico
Ragone, Concetta
Carriero, Maria Vincenza
Budillon, Alfredo
Botti, Gerardo
Ascierto, Paolo Antonio
Mancini, Rita
Ciliberto, Gennaro
author_facet Fattore, Luigi
Ruggiero, Ciro Francesco
Pisanu, Maria Elena
Liguoro, Domenico
Cerri, Andrea
Costantini, Susan
Capone, Francesca
Acunzo, Mario
Romano, Giulia
Nigita, Giovanni
Mallardo, Domenico
Ragone, Concetta
Carriero, Maria Vincenza
Budillon, Alfredo
Botti, Gerardo
Ascierto, Paolo Antonio
Mancini, Rita
Ciliberto, Gennaro
author_sort Fattore, Luigi
collection PubMed
description Drug resistance imposes severe limitations to the efficacy of targeted therapy in BRAF-mutated metastatic melanoma. Although this issue has been mitigated by the development of combination therapies with BRAF plus MEK inhibitors, drug resistance inevitably occurs with time and results in clinical recurrences and untreatable disease. Hence, there is strong need of developing new combination therapies and non-invasive diagnostics for the early identification of drug-resistant patients. We report here that the development of drug resistance to BRAFi is dominated by a dynamic deregulation of a large population of miRNAs, leading to the alteration of cell intrinsic proliferation and survival pathways, as well as of proinflammatory and proangiogenic cues, where a prominent role is played by the miR-199b-5p/VEGF axis. Significant alterations of miRNA expression levels are detectable in tumor biopsies and plasma from patients after disease recurrence. Targeting these alterations blunts the development of drug resistance.
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spelling pubmed-67481022019-09-18 Reprogramming miRNAs global expression orchestrates development of drug resistance in BRAF mutated melanoma Fattore, Luigi Ruggiero, Ciro Francesco Pisanu, Maria Elena Liguoro, Domenico Cerri, Andrea Costantini, Susan Capone, Francesca Acunzo, Mario Romano, Giulia Nigita, Giovanni Mallardo, Domenico Ragone, Concetta Carriero, Maria Vincenza Budillon, Alfredo Botti, Gerardo Ascierto, Paolo Antonio Mancini, Rita Ciliberto, Gennaro Cell Death Differ Article Drug resistance imposes severe limitations to the efficacy of targeted therapy in BRAF-mutated metastatic melanoma. Although this issue has been mitigated by the development of combination therapies with BRAF plus MEK inhibitors, drug resistance inevitably occurs with time and results in clinical recurrences and untreatable disease. Hence, there is strong need of developing new combination therapies and non-invasive diagnostics for the early identification of drug-resistant patients. We report here that the development of drug resistance to BRAFi is dominated by a dynamic deregulation of a large population of miRNAs, leading to the alteration of cell intrinsic proliferation and survival pathways, as well as of proinflammatory and proangiogenic cues, where a prominent role is played by the miR-199b-5p/VEGF axis. Significant alterations of miRNA expression levels are detectable in tumor biopsies and plasma from patients after disease recurrence. Targeting these alterations blunts the development of drug resistance. Nature Publishing Group UK 2018-09-25 2019-07 /pmc/articles/PMC6748102/ /pubmed/30254376 http://dx.doi.org/10.1038/s41418-018-0205-5 Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Fattore, Luigi
Ruggiero, Ciro Francesco
Pisanu, Maria Elena
Liguoro, Domenico
Cerri, Andrea
Costantini, Susan
Capone, Francesca
Acunzo, Mario
Romano, Giulia
Nigita, Giovanni
Mallardo, Domenico
Ragone, Concetta
Carriero, Maria Vincenza
Budillon, Alfredo
Botti, Gerardo
Ascierto, Paolo Antonio
Mancini, Rita
Ciliberto, Gennaro
Reprogramming miRNAs global expression orchestrates development of drug resistance in BRAF mutated melanoma
title Reprogramming miRNAs global expression orchestrates development of drug resistance in BRAF mutated melanoma
title_full Reprogramming miRNAs global expression orchestrates development of drug resistance in BRAF mutated melanoma
title_fullStr Reprogramming miRNAs global expression orchestrates development of drug resistance in BRAF mutated melanoma
title_full_unstemmed Reprogramming miRNAs global expression orchestrates development of drug resistance in BRAF mutated melanoma
title_short Reprogramming miRNAs global expression orchestrates development of drug resistance in BRAF mutated melanoma
title_sort reprogramming mirnas global expression orchestrates development of drug resistance in braf mutated melanoma
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6748102/
https://www.ncbi.nlm.nih.gov/pubmed/30254376
http://dx.doi.org/10.1038/s41418-018-0205-5
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