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The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer
Cyclin-dependent kinases (CDKs) are serine/threonine kinases whose catalytic activities are regulated by interactions with cyclins and CDK inhibitors (CKIs). CDKs are key regulatory enzymes involved in cell proliferation through regulating cell-cycle checkpoints and transcriptional events in respons...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139603/ https://www.ncbi.nlm.nih.gov/pubmed/32183020 http://dx.doi.org/10.3390/ijms21061960 |
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author | Ding, Lei Cao, Jiaqi Lin, Wen Chen, Hongjian Xiong, Xianhui Ao, Hongshun Yu, Min Lin, Jie Cui, Qinghua |
author_facet | Ding, Lei Cao, Jiaqi Lin, Wen Chen, Hongjian Xiong, Xianhui Ao, Hongshun Yu, Min Lin, Jie Cui, Qinghua |
author_sort | Ding, Lei |
collection | PubMed |
description | Cyclin-dependent kinases (CDKs) are serine/threonine kinases whose catalytic activities are regulated by interactions with cyclins and CDK inhibitors (CKIs). CDKs are key regulatory enzymes involved in cell proliferation through regulating cell-cycle checkpoints and transcriptional events in response to extracellular and intracellular signals. Not surprisingly, the dysregulation of CDKs is a hallmark of cancers, and inhibition of specific members is considered an attractive target in cancer therapy. In breast cancer (BC), dual CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, combined with other agents, were approved by the Food and Drug Administration (FDA) recently for the treatment of hormone receptor positive (HR+) advanced or metastatic breast cancer (A/MBC), as well as other sub-types of breast cancer. Furthermore, ongoing studies identified more selective CDK inhibitors as promising clinical targets. In this review, we focus on the roles of CDKs in driving cell-cycle progression, cell-cycle checkpoints, and transcriptional regulation, a highlight of dysregulated CDK activation in BC. We also discuss the most relevant CDK inhibitors currently in clinical BC trials, with special emphasis on CDK4/6 inhibitors used for the treatment of estrogen receptor-positive (ER+)/human epidermal growth factor 2-negative (HER2−) M/ABC patients, as well as more emerging precise therapeutic strategies, such as combination therapies and microRNA (miRNA) therapy. |
format | Online Article Text |
id | pubmed-7139603 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-71396032020-04-10 The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer Ding, Lei Cao, Jiaqi Lin, Wen Chen, Hongjian Xiong, Xianhui Ao, Hongshun Yu, Min Lin, Jie Cui, Qinghua Int J Mol Sci Review Cyclin-dependent kinases (CDKs) are serine/threonine kinases whose catalytic activities are regulated by interactions with cyclins and CDK inhibitors (CKIs). CDKs are key regulatory enzymes involved in cell proliferation through regulating cell-cycle checkpoints and transcriptional events in response to extracellular and intracellular signals. Not surprisingly, the dysregulation of CDKs is a hallmark of cancers, and inhibition of specific members is considered an attractive target in cancer therapy. In breast cancer (BC), dual CDK4/6 inhibitors, palbociclib, ribociclib, and abemaciclib, combined with other agents, were approved by the Food and Drug Administration (FDA) recently for the treatment of hormone receptor positive (HR+) advanced or metastatic breast cancer (A/MBC), as well as other sub-types of breast cancer. Furthermore, ongoing studies identified more selective CDK inhibitors as promising clinical targets. In this review, we focus on the roles of CDKs in driving cell-cycle progression, cell-cycle checkpoints, and transcriptional regulation, a highlight of dysregulated CDK activation in BC. We also discuss the most relevant CDK inhibitors currently in clinical BC trials, with special emphasis on CDK4/6 inhibitors used for the treatment of estrogen receptor-positive (ER+)/human epidermal growth factor 2-negative (HER2−) M/ABC patients, as well as more emerging precise therapeutic strategies, such as combination therapies and microRNA (miRNA) therapy. MDPI 2020-03-13 /pmc/articles/PMC7139603/ /pubmed/32183020 http://dx.doi.org/10.3390/ijms21061960 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 Ding, Lei Cao, Jiaqi Lin, Wen Chen, Hongjian Xiong, Xianhui Ao, Hongshun Yu, Min Lin, Jie Cui, Qinghua The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer |
title | The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer |
title_full | The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer |
title_fullStr | The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer |
title_full_unstemmed | The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer |
title_short | The Roles of Cyclin-Dependent Kinases in Cell-Cycle Progression and Therapeutic Strategies in Human Breast Cancer |
title_sort | roles of cyclin-dependent kinases in cell-cycle progression and therapeutic strategies in human breast cancer |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7139603/ https://www.ncbi.nlm.nih.gov/pubmed/32183020 http://dx.doi.org/10.3390/ijms21061960 |
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