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CDK9 inhibitors in acute myeloid leukemia
Current treatment for acute myeloid leukemia (AML) is less than optimal, but increased understanding of disease pathobiology and genomics has led to clinical investigation of novel targeted therapies and rational combinations. Targeting the cyclin-dependent kinase 9 (CDK9) pathway, which is dysregul...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824552/ https://www.ncbi.nlm.nih.gov/pubmed/29471852 http://dx.doi.org/10.1186/s13046-018-0704-8 |
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author | Boffo, Silvia Damato, Angela Alfano, Luigi Giordano, Antonio |
author_facet | Boffo, Silvia Damato, Angela Alfano, Luigi Giordano, Antonio |
author_sort | Boffo, Silvia |
collection | PubMed |
description | Current treatment for acute myeloid leukemia (AML) is less than optimal, but increased understanding of disease pathobiology and genomics has led to clinical investigation of novel targeted therapies and rational combinations. Targeting the cyclin-dependent kinase 9 (CDK9) pathway, which is dysregulated in AML, is an attractive approach. Inhibition of CDK9 leads to downregulation of cell survival genes regulated by super enhancers such as MCL-1, MYC, and cyclin D1. As CDK9 inhibitors are nonselective, predictive biomarkers that may help identify patients most likely to respond to CDK9 inhibitors are now being utilized, with the goal of improving efficacy and safety. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0704-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5824552 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-58245522018-02-26 CDK9 inhibitors in acute myeloid leukemia Boffo, Silvia Damato, Angela Alfano, Luigi Giordano, Antonio J Exp Clin Cancer Res Review Current treatment for acute myeloid leukemia (AML) is less than optimal, but increased understanding of disease pathobiology and genomics has led to clinical investigation of novel targeted therapies and rational combinations. Targeting the cyclin-dependent kinase 9 (CDK9) pathway, which is dysregulated in AML, is an attractive approach. Inhibition of CDK9 leads to downregulation of cell survival genes regulated by super enhancers such as MCL-1, MYC, and cyclin D1. As CDK9 inhibitors are nonselective, predictive biomarkers that may help identify patients most likely to respond to CDK9 inhibitors are now being utilized, with the goal of improving efficacy and safety. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13046-018-0704-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-23 /pmc/articles/PMC5824552/ /pubmed/29471852 http://dx.doi.org/10.1186/s13046-018-0704-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Review Boffo, Silvia Damato, Angela Alfano, Luigi Giordano, Antonio CDK9 inhibitors in acute myeloid leukemia |
title | CDK9 inhibitors in acute myeloid leukemia |
title_full | CDK9 inhibitors in acute myeloid leukemia |
title_fullStr | CDK9 inhibitors in acute myeloid leukemia |
title_full_unstemmed | CDK9 inhibitors in acute myeloid leukemia |
title_short | CDK9 inhibitors in acute myeloid leukemia |
title_sort | cdk9 inhibitors in acute myeloid leukemia |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824552/ https://www.ncbi.nlm.nih.gov/pubmed/29471852 http://dx.doi.org/10.1186/s13046-018-0704-8 |
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