Journal
EXPERT OPINION ON INVESTIGATIONAL DRUGS
Volume 23, Issue 3, Pages 295-304Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/13543784.2014.867017
Keywords
cancer; CDK inhibitors; cyclin D1; cyclin-dependent kinase
Categories
Funding
- NIH [R01CA07 0896, R01CA075503, R01CA132115, R01CA086072, R01C A137494]
- Kimmel Cancer Center NIH Cancer Center Core grant [P30CA56036]
- Dr. Ralph and Marian C. Falk Medical Research Trust
- Breast Cancer Research Foundation
- Pennsylvania Department of Health
- PAPIIT-UNAM [IN219613]
- Instituto Cientifico Pfizer, Mexico
- POSDOC-UNAM
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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.
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