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The multifaceted anti-cancer effects of BRAF-inhibitors

The BRAF gene is commonly involved in normal processes of cell growth and differentiation. The BRAF (V600E) mutation is found in several human cancer, causing an increase of cell proliferation due to a modification of the ERK/MAPK-signal cascade. In particular, BRAFV600E mutation is found in those m...

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Autores principales: Croce, Laura, Coperchini, Francesca, Magri, Flavia, Chiovato, Luca, Rotondi, Mario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859927/
https://www.ncbi.nlm.nih.gov/pubmed/31762942
http://dx.doi.org/10.18632/oncotarget.27304
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author Croce, Laura
Coperchini, Francesca
Magri, Flavia
Chiovato, Luca
Rotondi, Mario
author_facet Croce, Laura
Coperchini, Francesca
Magri, Flavia
Chiovato, Luca
Rotondi, Mario
author_sort Croce, Laura
collection PubMed
description The BRAF gene is commonly involved in normal processes of cell growth and differentiation. The BRAF (V600E) mutation is found in several human cancer, causing an increase of cell proliferation due to a modification of the ERK/MAPK-signal cascade. In particular, BRAFV600E mutation is found in those melanoma or thyroid cancer refractory to the common therapy and with a more aggressive phenotype. BRAF V600E was found to influence the composition of the so-called tumour microenvironment modulating both solid (immune-cell infiltration) and soluble (chemokines) mediators, which balance characterize the ultimate behaviour of the tumour, making it more or less aggressive. In particular, the presence of BRAFV600E mutation would be associated with a change of this balance to a more aggressive phenotype of the tumour and a worse prognosis. The investigation of the possible modulation of those components of tumour microenvironment is nowadays object of several studies as a new potential target therapy in those more complicated cases. At present several clinical trials both in melanoma and thyroid cancer are using BRAF-inhibitors with encouraging results, which are derived also from numerous in vitro pre-clinical studies aimed at evaluate the possible modulation of immune-cell density and of specific pro-tumorigenic chemokine secretion (CXCL8 and CCL2) by several BRAF-inhibitors in the context of melanoma and thyroid cancer. This review will encompass in vitro and in vivo studies which investigated the modulation of the tumour microenvironment by BRAF-inhibitors, highlighting also the most recent clinical trials with a specific focus on melanoma and thyroid cancer.
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spelling pubmed-68599272019-11-22 The multifaceted anti-cancer effects of BRAF-inhibitors Croce, Laura Coperchini, Francesca Magri, Flavia Chiovato, Luca Rotondi, Mario Oncotarget Review The BRAF gene is commonly involved in normal processes of cell growth and differentiation. The BRAF (V600E) mutation is found in several human cancer, causing an increase of cell proliferation due to a modification of the ERK/MAPK-signal cascade. In particular, BRAFV600E mutation is found in those melanoma or thyroid cancer refractory to the common therapy and with a more aggressive phenotype. BRAF V600E was found to influence the composition of the so-called tumour microenvironment modulating both solid (immune-cell infiltration) and soluble (chemokines) mediators, which balance characterize the ultimate behaviour of the tumour, making it more or less aggressive. In particular, the presence of BRAFV600E mutation would be associated with a change of this balance to a more aggressive phenotype of the tumour and a worse prognosis. The investigation of the possible modulation of those components of tumour microenvironment is nowadays object of several studies as a new potential target therapy in those more complicated cases. At present several clinical trials both in melanoma and thyroid cancer are using BRAF-inhibitors with encouraging results, which are derived also from numerous in vitro pre-clinical studies aimed at evaluate the possible modulation of immune-cell density and of specific pro-tumorigenic chemokine secretion (CXCL8 and CCL2) by several BRAF-inhibitors in the context of melanoma and thyroid cancer. This review will encompass in vitro and in vivo studies which investigated the modulation of the tumour microenvironment by BRAF-inhibitors, highlighting also the most recent clinical trials with a specific focus on melanoma and thyroid cancer. Impact Journals LLC 2019-11-12 /pmc/articles/PMC6859927/ /pubmed/31762942 http://dx.doi.org/10.18632/oncotarget.27304 Text en http://creativecommons.org/licenses/by/3.0/ Copyright: Croce et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Review
Croce, Laura
Coperchini, Francesca
Magri, Flavia
Chiovato, Luca
Rotondi, Mario
The multifaceted anti-cancer effects of BRAF-inhibitors
title The multifaceted anti-cancer effects of BRAF-inhibitors
title_full The multifaceted anti-cancer effects of BRAF-inhibitors
title_fullStr The multifaceted anti-cancer effects of BRAF-inhibitors
title_full_unstemmed The multifaceted anti-cancer effects of BRAF-inhibitors
title_short The multifaceted anti-cancer effects of BRAF-inhibitors
title_sort multifaceted anti-cancer effects of braf-inhibitors
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6859927/
https://www.ncbi.nlm.nih.gov/pubmed/31762942
http://dx.doi.org/10.18632/oncotarget.27304
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