Targeting CDK6 in cancer: State of the art and new insights

Cyclin-dependent kinase 6 (CDK6) plays a vital role in regulating the progression of the cell cycle. More recently, CDK6 has also been shown to have a transcriptional role in tumor angiogenesis. Up-regulated CDK6 activity is associated with the development of several types of cancers. While CDK6 is...

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Bibliographic Details
Published in:Cell cycle (Georgetown, Tex.) Tex.), 2015-10, Vol.14 (20), p.3220-3230
Main Authors: Tadesse, Solomon, Yu, Mingfeng, Kumarasiri, Malika, Le, Bich Thuy, Wang, Shudong
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
cell cycle
Cell Cycle - drug effects
Cell Cycle - physiology
Crystallography, X-Ray
cyclin-dependent kinase
Cyclin-Dependent Kinase 6 - antagonists & inhibitors
Cyclin-Dependent Kinase 6 - chemistry
Cyclin-Dependent Kinase 6 - metabolism
Drug Delivery Systems - methods
Drug Delivery Systems - trends
drug discovery
Humans
inhibitor design
Neoplasms - drug therapy
Neoplasms - metabolism
oncogene and tumor suppressor
Protein Structure, Secondary
Review
targeted cancer therapy
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Summary:Cyclin-dependent kinase 6 (CDK6) plays a vital role in regulating the progression of the cell cycle. More recently, CDK6 has also been shown to have a transcriptional role in tumor angiogenesis. Up-regulated CDK6 activity is associated with the development of several types of cancers. While CDK6 is over-expressed in cancer cells, it has a low detectable level in non-cancerous cells and CDK6-null mice develop normally, suggesting a specific oncogenic role of CDK6, and that its inhibition may represent an ideal mechanism-based and low toxic therapeutic strategy in cancer treatment. Identification of selective small molecule inhibitors of CDK6 is thus needed for drug development. Herein, we review the latest understandings of the biological regulation and oncogenic roles of CDK6. The potential clinical relevance of CDK6 inhibition, the progress in the development of small-molecule CDK6 inhibitors and the rational design of potential selective CDK6 inhibitors are also discussed.
ISSN:1538-4101
1551-4005
DOI:10.1080/15384101.2015.1084445