Abstract
Cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) and their activating partners, D-type cyclins, link the extracellular environment with the core cell cycle machinery. Constitutive activation of cyclin D–CDK4/6 represents the driving force of tumorigenesis in several cancer types. Small-molecule inhibitors of CDK4/6 have been used with great success in the treatment of hormone receptor–positive breast cancers and are in clinical trials for many other tumor types. Unexpectedly, recent work indicates that inhibition of CDK4/6 affects a wide range of cellular functions such as tumor cell metabolism and antitumor immunity. We discuss how recent advances in understanding CDK4/6 biology are opening new avenues for the future use of cyclin D–CDK4/6 inhibitors in cancer treatment.
Publication types
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Research Support, N.I.H., Extramural
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Review
MeSH terms
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Animals
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Antineoplastic Combined Chemotherapy Protocols / pharmacology
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Carcinogenesis
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Cell Proliferation / drug effects
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Cellular Senescence
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Clinical Trials as Topic
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Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
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Cyclin-Dependent Kinase 4 / metabolism*
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Cyclin-Dependent Kinase 6 / antagonists & inhibitors*
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Cyclin-Dependent Kinase 6 / metabolism*
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Drug Resistance, Neoplasm
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Drug Synergism
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Humans
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Neoplasms / drug therapy*
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Neoplasms / immunology
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Neoplasms / metabolism
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Neoplasms / pathology
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use
Substances
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Cyclin-Dependent Kinase 4
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Cyclin-Dependent Kinase 6