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. 2017 Mar;9(1):26-33.
doi: 10.1007/s12609-017-0232-0. Epub 2017 Feb 1.

CDK4/6 Inhibition in Breast Cancer: Mechanisms of Response and Treatment Failure

Ana C Garrido-Castro  1 , Shom Goel  1
Affiliations

CDK4/6 Inhibition in Breast Cancer: Mechanisms of Response and Treatment Failure

Ana C Garrido-Castro et al. Curr Breast Cancer Rep. 2017 Mar.

Abstract

Purpose of review: To describe the role of D-type cyclins and CDKs 4 and 6 in breast cancer, and to discuss potential biomarkers for sensitivity or resistance to CDK4/6 inhibitors.

Recent findings: A small number of preclinical and clinical studies have explored potential mechanisms of CDK4/6 inhibitor response and resistance in breast cancer. Putative markers of response include ER-positivity, luminal patterns of gene expression, high cyclin D1 levels, and low p16 levels. Possible resistance mechanisms include loss of Rb function, overexpression/amplification of cyclin E, and CDK6 amplification. Most these remain speculative and have not been validated in clinical specimens.

Summary: If early successes with CDK4/6 inhibitors are to be capitalized upon, it is critical that our understanding of CDK4/6 biology in breast cancer extends beyond its current rudimentary state. Only then we will be able to develop rational therapeutic combinations that further enhance the efficacy of these agents.

Keywords: CDK4/6; breast cancer; cyclin; drug resistance; estrogen receptor.

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Conflict of interest statement

Conflict of Interest Ana C. Garrido-Castro declares no conflict of interest.

Figures

Figure 1
Figure 1
The role of cyclins/cyclin-dependent kinases (CDK) in cell-cycle progression and the crosstalk with oncogenic signaling pathways.
See this image and copyright information in PMC

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