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The Role of BRAF in Metastatic Colorectal Carcinoma–Past, Present, and Future

With a global incidence of 1.8 million cases, colorectal cancer represents one of the most common cancers worldwide. Despite impressive improvements in treatment efficacy through cytotoxic and biological agents, the cancer-related death burden of metastatic colorectal cancer (mCRC) is still high. mC...

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Autores principales: Djanani, Angela, Eller, Silvia, Öfner, Dietmar, Troppmair, Jakob, Maglione, Manuel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729567/
https://www.ncbi.nlm.nih.gov/pubmed/33256240
http://dx.doi.org/10.3390/ijms21239001
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author Djanani, Angela
Eller, Silvia
Öfner, Dietmar
Troppmair, Jakob
Maglione, Manuel
author_facet Djanani, Angela
Eller, Silvia
Öfner, Dietmar
Troppmair, Jakob
Maglione, Manuel
author_sort Djanani, Angela
collection PubMed
description With a global incidence of 1.8 million cases, colorectal cancer represents one of the most common cancers worldwide. Despite impressive improvements in treatment efficacy through cytotoxic and biological agents, the cancer-related death burden of metastatic colorectal cancer (mCRC) is still high. mCRC is not a genetically homogenous disease and various mutations influence disease development. Up to 12% of mCRC patients harbor mutations of the signal transduction molecule BRAF, the most prominent being BRAF(V600E). In mCRC, BRAF(V600E) mutation is a well-known negative prognostic factor, and is associated with a dismal prognosis. The currently approved treatments for BRAF-mutated mCRC patients are of little impact, and there is no treatment option superior to others. However, the gradual molecular understanding over the last decades of the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway, resulted in the development of new therapeutic strategies targeting the involved molecules. Recently published and ongoing studies administering a combination of different inhibitors (e.g., BRAF, MEK, and EGFR) showed promising results and represent the new standard of care. In this review, we present, both, the molecular and clinical aspects of BRAF-mutated mCRC patients, and provide an update on the current and future treatment approaches that might direct the therapy of mCRC in a new era.
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spelling pubmed-77295672020-12-12 The Role of BRAF in Metastatic Colorectal Carcinoma–Past, Present, and Future Djanani, Angela Eller, Silvia Öfner, Dietmar Troppmair, Jakob Maglione, Manuel Int J Mol Sci Review With a global incidence of 1.8 million cases, colorectal cancer represents one of the most common cancers worldwide. Despite impressive improvements in treatment efficacy through cytotoxic and biological agents, the cancer-related death burden of metastatic colorectal cancer (mCRC) is still high. mCRC is not a genetically homogenous disease and various mutations influence disease development. Up to 12% of mCRC patients harbor mutations of the signal transduction molecule BRAF, the most prominent being BRAF(V600E). In mCRC, BRAF(V600E) mutation is a well-known negative prognostic factor, and is associated with a dismal prognosis. The currently approved treatments for BRAF-mutated mCRC patients are of little impact, and there is no treatment option superior to others. However, the gradual molecular understanding over the last decades of the extracellular signal-regulated kinase/mitogen-activated protein kinase pathway, resulted in the development of new therapeutic strategies targeting the involved molecules. Recently published and ongoing studies administering a combination of different inhibitors (e.g., BRAF, MEK, and EGFR) showed promising results and represent the new standard of care. In this review, we present, both, the molecular and clinical aspects of BRAF-mutated mCRC patients, and provide an update on the current and future treatment approaches that might direct the therapy of mCRC in a new era. MDPI 2020-11-26 /pmc/articles/PMC7729567/ /pubmed/33256240 http://dx.doi.org/10.3390/ijms21239001 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Djanani, Angela
Eller, Silvia
Öfner, Dietmar
Troppmair, Jakob
Maglione, Manuel
The Role of BRAF in Metastatic Colorectal Carcinoma–Past, Present, and Future
title The Role of BRAF in Metastatic Colorectal Carcinoma–Past, Present, and Future
title_full The Role of BRAF in Metastatic Colorectal Carcinoma–Past, Present, and Future
title_fullStr The Role of BRAF in Metastatic Colorectal Carcinoma–Past, Present, and Future
title_full_unstemmed The Role of BRAF in Metastatic Colorectal Carcinoma–Past, Present, and Future
title_short The Role of BRAF in Metastatic Colorectal Carcinoma–Past, Present, and Future
title_sort role of braf in metastatic colorectal carcinoma–past, present, and future
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729567/
https://www.ncbi.nlm.nih.gov/pubmed/33256240
http://dx.doi.org/10.3390/ijms21239001
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