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Breast Cancer Research
Published in: Breast Cancer Research 1/2016

Open Access 01-12-2016 | Review

Targeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancers

Authors: Richard S. Finn, Alexey Aleshin, Dennis J. Slamon

Published in: Breast Cancer Research | Issue 1/2016

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Abstract

Despite significant advances in early detection and treatment, breast cancer still remains a major cause of morbidity and mortality for women. Our understanding of the molecular heterogeneity of the disease has significantly expanded over the past decade and the role of cell cycle signaling in both breast cancer oncogenesis and anti-estrogen resistance has gained increasing attention. The mammalian cell cycle is driven by a complex interplay between cyclins and their associated cyclin-dependent kinase (CDK) partners, and dysregulation of this process is one of the hallmarks of cancer. Despite this, initial results with broadly acting CDK inhibitors were largely disappointing. However, recent preclinical and phase I/II clinical studies using a novel, oral, reversible CDK4/6 inhibitor, palbociclib (PD-0332991), have validated the role of CDK4/6 as a potential target in estrogen receptor-positive (ER+) breast cancers. This review highlights our current understanding of CDK signaling in both normal and malignant breast tissues, with special attention placed on recent clinical advances in inhibition of CDK4/6 in ER+ disease.
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Metadata
Title
Targeting the cyclin-dependent kinases (CDK) 4/6 in estrogen receptor-positive breast cancers
Authors
Richard S. Finn
Alexey Aleshin
Dennis J. Slamon
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2016
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-015-0661-5

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