CDK4 and CDK6 kinases: From basic science to cancer therapy

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 inhi...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2022-01, Vol.375 (6577), p.eabc1495-eabc1495
Main Authors: Fassl, Anne, Geng, Yan, Sicinski, Piotr
Format: Article
Language:English
Subjects:
Animal models
Animals
Antineoplastic Agents - adverse effects
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - pharmacology
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Biology
Breast cancer
Cancer
Cancer therapies
Carcinogenesis
Cell activation
Cell culture
Cell cycle
Cell division
Cell growth
Cell proliferation
Cell Proliferation - drug effects
Cellular Senescence
Chemical compounds
Chemical synthesis
Chemotherapy
Clinical trials
Clinical Trials as Topic
Cyclin D
Cyclin-dependent kinase
Cyclin-dependent kinase 4
Cyclin-Dependent Kinase 4 - antagonists & inhibitors
Cyclin-Dependent Kinase 4 - metabolism
Cyclin-Dependent Kinase 6 - antagonists & inhibitors
Cyclin-Dependent Kinase 6 - metabolism
Cyclin-dependent kinases
Cytostasis
Cytotoxicity
Drug development
Drug Resistance, Neoplasm
Drug Synergism
Endocrine therapy
Fractions
Health services
Humans
Immune checkpoint
Immune system
Immunity
Immunosuppressive agents
Inhibition
Inhibitors
Kinases
Metabolism
Metastases
Neoplasms - drug therapy
Neoplasms - immunology
Neoplasms - metabolism
Neoplasms - pathology
Patients
Pharmacology
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Receptors
Survival
Therapeutic targets
Tumor cells
Tumorigenesis
Tumors
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Description
Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.abc1495