Cyclin dependent kinase 4 and 6 inhibitors as novel therapeutic agents for targeted treatment of malignant mesothelioma

Malignant Mesothelioma (MM) is a rare and aggressive form of tumour that affects the lining of the internal organs for which current treatments have not been proven to be very effective. P16(INK4A) tumour suppressor encoding CDKN2A gene is often downregulated in MM. This protein is a cyclin dependen...

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Autores principales: Sobhani, Navid, Corona, Silvia P., Zanconati, Fabrizio, Generali, Daniele
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489646/
https://www.ncbi.nlm.nih.gov/pubmed/28680533
http://dx.doi.org/10.18632/genesandcancer.138
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author Sobhani, Navid
Corona, Silvia P.
Zanconati, Fabrizio
Generali, Daniele
author_facet Sobhani, Navid
Corona, Silvia P.
Zanconati, Fabrizio
Generali, Daniele
author_sort Sobhani, Navid
collection PubMed
description Malignant Mesothelioma (MM) is a rare and aggressive form of tumour that affects the lining of the internal organs for which current treatments have not been proven to be very effective. P16(INK4A) tumour suppressor encoding CDKN2A gene is often downregulated in MM. This protein is a cyclin dependent kinase 4 and 6 inhibitor, that normally phosphorylates RB1, which has to be un-phosphorylated in order to block cell-cycle at G1 in normal cells. Adding CDK inhibitor molecules to MM in pre-clinical studies has been proven to restore the normal function of p16(INK4A), blocking thereby MM cell cycle at G1. Future randomised phase III studies with CDK4/6 inhibitors in MM carrying relevant CDK4/6, cyclin D1/3 or p16 aberrations will be warranted.
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spelling pubmed-54896462017-07-05 Cyclin dependent kinase 4 and 6 inhibitors as novel therapeutic agents for targeted treatment of malignant mesothelioma Sobhani, Navid Corona, Silvia P. Zanconati, Fabrizio Generali, Daniele Genes Cancer Research Perspective Malignant Mesothelioma (MM) is a rare and aggressive form of tumour that affects the lining of the internal organs for which current treatments have not been proven to be very effective. P16(INK4A) tumour suppressor encoding CDKN2A gene is often downregulated in MM. This protein is a cyclin dependent kinase 4 and 6 inhibitor, that normally phosphorylates RB1, which has to be un-phosphorylated in order to block cell-cycle at G1 in normal cells. Adding CDK inhibitor molecules to MM in pre-clinical studies has been proven to restore the normal function of p16(INK4A), blocking thereby MM cell cycle at G1. Future randomised phase III studies with CDK4/6 inhibitors in MM carrying relevant CDK4/6, cyclin D1/3 or p16 aberrations will be warranted. Impact Journals LLC 2017-03 /pmc/articles/PMC5489646/ /pubmed/28680533 http://dx.doi.org/10.18632/genesandcancer.138 Text en Copyright: © 2017 Sobhani et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Research Perspective
Sobhani, Navid
Corona, Silvia P.
Zanconati, Fabrizio
Generali, Daniele
Cyclin dependent kinase 4 and 6 inhibitors as novel therapeutic agents for targeted treatment of malignant mesothelioma
title Cyclin dependent kinase 4 and 6 inhibitors as novel therapeutic agents for targeted treatment of malignant mesothelioma
title_full Cyclin dependent kinase 4 and 6 inhibitors as novel therapeutic agents for targeted treatment of malignant mesothelioma
title_fullStr Cyclin dependent kinase 4 and 6 inhibitors as novel therapeutic agents for targeted treatment of malignant mesothelioma
title_full_unstemmed Cyclin dependent kinase 4 and 6 inhibitors as novel therapeutic agents for targeted treatment of malignant mesothelioma
title_short Cyclin dependent kinase 4 and 6 inhibitors as novel therapeutic agents for targeted treatment of malignant mesothelioma
title_sort cyclin dependent kinase 4 and 6 inhibitors as novel therapeutic agents for targeted treatment of malignant mesothelioma
topic Research Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489646/
https://www.ncbi.nlm.nih.gov/pubmed/28680533
http://dx.doi.org/10.18632/genesandcancer.138
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