Abstract
The activity of cyclins and their associated cyclin-dependent kinases (CDKs) is frequently deranged in human cancers. For this reason, cyclin-CDK complexes have been considered as very promising therapeutic targets in human malignancies. An obvious concern, however, is whether blocking cyclin-CDK function would preferentially affect cancer cells, but not normal, non-transformed cells. Two recent reports addressed the requirement for cyclin D1-CDK4 kinase in mouse development versus in neoplasia. These studies documented that the kinase activity of cyclin D1-CDK complexes is largely dispensable for normal development, but it is critically required for the initiation and maintenance of mammary carcinomas. Here we summarize the lessons learned from mouse knockout experiments, and discuss the utility of CDK inhibitors in therapy of human cancers, and possibly of other diseases.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Cell Cycle / drug effects
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Cell Cycle / genetics
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Cell Transformation, Neoplastic / drug effects
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Cell Transformation, Neoplastic / genetics*
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Cell Transformation, Neoplastic / metabolism
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Cyclin-Dependent Kinases / antagonists & inhibitors*
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Cyclin-Dependent Kinases / genetics
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Cyclin-Dependent Kinases / metabolism
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Cyclins / genetics
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Cyclins / metabolism*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Enzyme Inhibitors / therapeutic use
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Humans
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Mammary Neoplasms, Animal / drug therapy
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Mammary Neoplasms, Animal / enzymology
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Mammary Neoplasms, Animal / genetics
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Mice
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Mice, Knockout / genetics
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Mice, Knockout / metabolism
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Molecular Structure
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Neoplasms / drug therapy*
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Neoplasms / enzymology*
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Neoplasms / genetics
Substances
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Cyclins
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Enzyme Inhibitors
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Cyclin-Dependent Kinases