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CDK9 as a Valuable Target in Cancer: From Natural Compounds Inhibitors to Current Treatment in Pediatric Soft Tissue Sarcomas

Cyclin-Dependent Kinases (CDKs) are well-known reliable targets for cancer treatment being often deregulated. Among them, since the transcription-associated CDK9 represents the sentry of cell transcriptional homeostasis, it can be a valuable target for managing cancers in which the transcriptional m...

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Autores principales: Cassandri, Matteo, Fioravanti, Rossella, Pomella, Silvia, Valente, Sergio, Rotili, Dante, Del Baldo, Giada, De Angelis, Biagio, Rota, Rossella, Mai, Antonello
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438590/
https://www.ncbi.nlm.nih.gov/pubmed/32903585
http://dx.doi.org/10.3389/fphar.2020.01230
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author Cassandri, Matteo
Fioravanti, Rossella
Pomella, Silvia
Valente, Sergio
Rotili, Dante
Del Baldo, Giada
De Angelis, Biagio
Rota, Rossella
Mai, Antonello
author_facet Cassandri, Matteo
Fioravanti, Rossella
Pomella, Silvia
Valente, Sergio
Rotili, Dante
Del Baldo, Giada
De Angelis, Biagio
Rota, Rossella
Mai, Antonello
author_sort Cassandri, Matteo
collection PubMed
description Cyclin-Dependent Kinases (CDKs) are well-known reliable targets for cancer treatment being often deregulated. Among them, since the transcription-associated CDK9 represents the sentry of cell transcriptional homeostasis, it can be a valuable target for managing cancers in which the transcriptional machinery is dysregulated by tumor-driver oncogenes. Here we give an overview of some natural compounds identified as CDK inhibitors with reported activity also against CDK9, that were taken as a model for the development of highly active synthetic anti-CDK9 agents. After, we summarize the data on CDK9 inhibition in a group of rare pediatric solid tumors such as rhabdomyosarcoma, Ewing’s sarcoma, synovial sarcoma and malignant rhabdoid tumors (soft tissue sarcomas), highlighting the more recent results in this field. Finally, we discuss the perspective and challenge of CDK9 modulation in cancer.
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spelling pubmed-74385902020-09-03 CDK9 as a Valuable Target in Cancer: From Natural Compounds Inhibitors to Current Treatment in Pediatric Soft Tissue Sarcomas Cassandri, Matteo Fioravanti, Rossella Pomella, Silvia Valente, Sergio Rotili, Dante Del Baldo, Giada De Angelis, Biagio Rota, Rossella Mai, Antonello Front Pharmacol Pharmacology Cyclin-Dependent Kinases (CDKs) are well-known reliable targets for cancer treatment being often deregulated. Among them, since the transcription-associated CDK9 represents the sentry of cell transcriptional homeostasis, it can be a valuable target for managing cancers in which the transcriptional machinery is dysregulated by tumor-driver oncogenes. Here we give an overview of some natural compounds identified as CDK inhibitors with reported activity also against CDK9, that were taken as a model for the development of highly active synthetic anti-CDK9 agents. After, we summarize the data on CDK9 inhibition in a group of rare pediatric solid tumors such as rhabdomyosarcoma, Ewing’s sarcoma, synovial sarcoma and malignant rhabdoid tumors (soft tissue sarcomas), highlighting the more recent results in this field. Finally, we discuss the perspective and challenge of CDK9 modulation in cancer. Frontiers Media S.A. 2020-08-13 /pmc/articles/PMC7438590/ /pubmed/32903585 http://dx.doi.org/10.3389/fphar.2020.01230 Text en Copyright © 2020 Cassandri, Fioravanti, Pomella, Valente, Rotili, Del Baldo, De Angelis, Rota and Mai http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Cassandri, Matteo
Fioravanti, Rossella
Pomella, Silvia
Valente, Sergio
Rotili, Dante
Del Baldo, Giada
De Angelis, Biagio
Rota, Rossella
Mai, Antonello
CDK9 as a Valuable Target in Cancer: From Natural Compounds Inhibitors to Current Treatment in Pediatric Soft Tissue Sarcomas
title CDK9 as a Valuable Target in Cancer: From Natural Compounds Inhibitors to Current Treatment in Pediatric Soft Tissue Sarcomas
title_full CDK9 as a Valuable Target in Cancer: From Natural Compounds Inhibitors to Current Treatment in Pediatric Soft Tissue Sarcomas
title_fullStr CDK9 as a Valuable Target in Cancer: From Natural Compounds Inhibitors to Current Treatment in Pediatric Soft Tissue Sarcomas
title_full_unstemmed CDK9 as a Valuable Target in Cancer: From Natural Compounds Inhibitors to Current Treatment in Pediatric Soft Tissue Sarcomas
title_short CDK9 as a Valuable Target in Cancer: From Natural Compounds Inhibitors to Current Treatment in Pediatric Soft Tissue Sarcomas
title_sort cdk9 as a valuable target in cancer: from natural compounds inhibitors to current treatment in pediatric soft tissue sarcomas
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438590/
https://www.ncbi.nlm.nih.gov/pubmed/32903585
http://dx.doi.org/10.3389/fphar.2020.01230
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