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Expert Opin Investig Drugs. 2014 Mar;23(3):295-304. doi: 10.1517/13543784.2014.867017. Epub 2014 Jan 3.

Overview of cyclins D1 function in cancer and the CDK inhibitor landscape: past and present.

Author information

1
Thomas Jefferson University & Hospital, Department of Cancer Biology , 233 South 10th Street, Philadelphia, PA 19107 , USA.

Abstract

INTRODUCTION:

Intensive efforts, over the last decade, have been made to inhibit the kinase activity of cyclins that act as mediators during cell-cycle progression. Activation of the cyclin D1 oncogene, often by amplification or rearrangement, is a major driver of multiple types of human tumors including breast and squamous cell cancers, B-cell lymphoma, myeloma and parathyroid adenoma.

AREAS COVERED:

In this review, the authors summarize the activity of cyclins and cyclin-dependent kinases in cell-cycle progression and transcription. They focus on cyclin D1/CDK4/CDK6, a central mediator in the transition from G1 to S phase. Furthermore, the authors discuss the first generation of pan-cyclin-dependent kinase inhibitors that failed to meet expectation and discuss, in detail, the second generation of highly specific cyclin D1/CDK4/CDK6 inhibitors that are proving to be more efficacious.

EXPERT OPINION:

The mechanism by which cyclin D1 drives tumorigenesis may be dependent on kinase and kinase-independent functions. Further evidence is necessary to delineate the roles of cyclin D1 in early pre-neoplastic lesions where its overexpression may promote genomic instability in a kinase-independent manner.

PMID:
24387133
DOI:
10.1517/13543784.2014.867017
[Indexed for MEDLINE]

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