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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...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2012
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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. |
format | Online Article Text |
id | pubmed-3246694 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
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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