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CDK4/6 inhibitors in breast cancer

Dukelow, Tim, Kishan, Divya, Khasraw, Mustafa and Murphy, Conleth G. 2015, CDK4/6 inhibitors in breast cancer, Anti-cancer drugs, vol. 26, no. 8, pp. 797-806, doi: 10.1097/CAD.0000000000000249.

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Title CDK4/6 inhibitors in breast cancer
Author(s) Dukelow, Tim
Kishan, Divya
Khasraw, Mustafa
Murphy, Conleth G.
Journal name Anti-cancer drugs
Volume number 26
Issue number 8
Start page 797
End page 806
Total pages 7
Publisher Lippincott Williams & Wilkins
Place of publication Philadelphia, Pa.
Publication date 2015-09
ISSN 1473-5741
Keyword(s) animals
antineoplastic agents
breast neoplasms
clinical trials as topic
cyclin-dependent kinase 4
cyclin-dependent kinase 6
female
humans
protein kinase inhibitors
Summary Deregulation of the cyclin-dependent kinase (CDK) 4/6-retinoblastoma (RB) axis can occur through a number of mechanisms and contributes towards the unrestrained growth witnessed in a variety of cancers including breast cancers. Recent years have seen the development of selective CDK4/6 inhibitors, which have delivered promising preclinical and clinical results in breast cancer and other tumours. A number of trials assessing antitumour efficacy in various disease settings and combinations are ongoing. The cyclin D1-CDK-Rb axis and its role in the cell cycle of normal and cancer cells are delineated. The early pan-CDK inhibitor flavopiridol and subsequent preclinical and clinical development of selective CDK4/6 inhibitors are described. Ongoing studies in breast cancer with novel CDK4/6 inhibitors (palbociclib, abemaciclib and ribociclib) are explored. A literature search of these topics was performed through PubMed. Abstracts from major oncology meetings were also reviewed. Selective CDK4/6 inhibitors, as represented by the competing compounds currently in clinical development, comprise a novel, safe and, thus far, promisingly efficacious group of drugs. Considerable resources are being devoted towards exploring the efficacy of these drugs in combination with endocrine therapies, an approach that has yielded encouraging results and accelerated approval by the US Food and Drugs Administration for one of these agents (palbociclib). The results of confirmatory phase 3 trials are, however, awaited. We discuss further therapy combinations in development and highlight potential areas for caution including the potential for antagonistic interactions with cytotoxic chemotherapies.
Language eng
DOI 10.1097/CAD.0000000000000249
Field of Research 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
1115 Pharmacology And Pharmaceutical Sciences
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2015, Wolters Kluwer Health
Persistent URL http://hdl.handle.net/10536/DRO/DU:30075791

Document type: Journal Article
Collection: School of Medicine
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