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Targeting the Cellular Signaling: BRAF Inhibition and Beyond for the Treatment of Metastatic Malignant Melanoma

Although advances in cytotoxic treatments have been obtained in several neoplasias, in metastatic melanoma there was no drug able to significantly change the natural history of the disease in the last 30 years. In the last decade, translational research identified important mechanisms in malignant t...

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Detalles Bibliográficos
Autores principales: Ades, Felipe, Metzger-Filho, Otto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246694/
https://www.ncbi.nlm.nih.gov/pubmed/22216021
http://dx.doi.org/10.1155/2012/259170
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author Ades, Felipe
Metzger-Filho, Otto
author_facet Ades, Felipe
Metzger-Filho, Otto
author_sort Ades, Felipe
collection PubMed
description Although advances in cytotoxic treatments have been obtained in several neoplasias, in metastatic melanoma there was no drug able to significantly change the natural history of the disease in the last 30 years. In the last decade, translational research identified important mechanisms in malignant transformation, invasion, and progression. Signaling pathways can be abnormally activated by oncogenes. The identification of oncogenic mutated kinases implicated in this process provides an opportunity for new target therapies. The melanoma dependence on BRAF-mutated kinase allowed the development of inhibitors that produced major responses in clinical trials. This is the beginning of a novel class of drugs in metastatic melanoma; the identification of the transduction signaling networking and other “druggable” kinases is in active research. In this paper, we discuss the ongoing research on cellular signaling inhibition, resistance mechanisms, and strategies to overcome treatment failure.
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spelling pubmed-32466942012-01-03 Targeting the Cellular Signaling: BRAF Inhibition and Beyond for the Treatment of Metastatic Malignant Melanoma Ades, Felipe Metzger-Filho, Otto Dermatol Res Pract Review Article Although advances in cytotoxic treatments have been obtained in several neoplasias, in metastatic melanoma there was no drug able to significantly change the natural history of the disease in the last 30 years. In the last decade, translational research identified important mechanisms in malignant transformation, invasion, and progression. Signaling pathways can be abnormally activated by oncogenes. The identification of oncogenic mutated kinases implicated in this process provides an opportunity for new target therapies. The melanoma dependence on BRAF-mutated kinase allowed the development of inhibitors that produced major responses in clinical trials. This is the beginning of a novel class of drugs in metastatic melanoma; the identification of the transduction signaling networking and other “druggable” kinases is in active research. In this paper, we discuss the ongoing research on cellular signaling inhibition, resistance mechanisms, and strategies to overcome treatment failure. Hindawi Publishing Corporation 2012 2011-12-15 /pmc/articles/PMC3246694/ /pubmed/22216021 http://dx.doi.org/10.1155/2012/259170 Text en Copyright © 2012 F. Ades and O. Metzger-Filho. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Ades, Felipe
Metzger-Filho, Otto
Targeting the Cellular Signaling: BRAF Inhibition and Beyond for the Treatment of Metastatic Malignant Melanoma
title Targeting the Cellular Signaling: BRAF Inhibition and Beyond for the Treatment of Metastatic Malignant Melanoma
title_full Targeting the Cellular Signaling: BRAF Inhibition and Beyond for the Treatment of Metastatic Malignant Melanoma
title_fullStr Targeting the Cellular Signaling: BRAF Inhibition and Beyond for the Treatment of Metastatic Malignant Melanoma
title_full_unstemmed Targeting the Cellular Signaling: BRAF Inhibition and Beyond for the Treatment of Metastatic Malignant Melanoma
title_short Targeting the Cellular Signaling: BRAF Inhibition and Beyond for the Treatment of Metastatic Malignant Melanoma
title_sort targeting the cellular signaling: braf inhibition and beyond for the treatment of metastatic malignant melanoma
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3246694/
https://www.ncbi.nlm.nih.gov/pubmed/22216021
http://dx.doi.org/10.1155/2012/259170
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