Cyclin D as a therapeutic target in cancer

  title={Cyclin D as a therapeutic target in cancer},
  author={Elizabeth A. Musgrove and C Elizabeth Caldon and Jane Barraclough and Andrew Stone and Robert Lyndsay Sutherland},
  journal={Nature Reviews Cancer},
Cyclin D1, and to a lesser extent the other D-type cyclins, is frequently deregulated in cancer and is a biomarker of cancer phenotype and disease progression. The ability of these cyclins to activate the cyclin-dependent kinases (CDKs) CDK4 and CDK6 is the most extensively documented mechanism for their oncogenic actions and provides an attractive therapeutic target. Is this an effective means of targeting the cyclin D oncogenes, and how might the patient subgroups that are most likely to… 

Targeting the CDK4/6 Pathway in Breast Cancer

Preclinical and clinical data suggest that CDK4/6 inhibitors might be particularly useful in patients with hormone receptor-positive or HER2-positive tumors, while the role of such inhibitors in triple-negative breast cancer is still controversial.

Cyclin D1, cancer progression, and opportunities in cancer treatment

This review discusses cyclin D1 transcriptional, translational, and post-translational regulations and its biological function with a particular focus on the mechanisms that result in its dysregulation in human cancers.

An update on the implications of cyclin D1 in melanomas

This review examines data published on upregulation of the CCND1 gene and cyclin D1 protein in the melanoma setting, focusing on the pathways and molecular mechanisms involved in the activation of the gene and on the clinical and therapeutic implications.

Degradation strategy of cyclin D1 in cancer cells and the potential clinical application

A possible photodynamic therapy strategy that is based on the above concrete combination mode of FBX4 and cyclin D1 for treating superficial cancer is proposed.

Cyclins and cell cycle control in cancer and disease.

Evidence is examined that examines the functional roles that cyclin D1 may play in cancer with an emphasis on other cyclin family members that also may contribute to cancer and disease in a similar fashion.

Cyclin Kinase Inhibitors in Breast Cancer: From Bench to Bedside

This review gathers the results of the most recent clinical trials of CDK inhibitors for breast cancer, and outlines their potential as anticancer therapy.

CDK4/6 and MAPK—Crosstalk as Opportunity for Cancer Treatment

This work focuses on the cell cycle kinase CDK6 and on the MAPK pathway and on their interplay and provides an overview on clinical studies examining the effects of combinational treatments currently explored for several cancer types.

Targeting CDK4 and CDK6 in cancer

How CDK4 and CDK6 inhibitors are only now beginning to fully understand their mechanisms of action is described and a new framework for conceptualizing their activity is provided, which might enable expansion of the clinical opportunities of these agents.



Cyclin D1 in breast cancer pathogenesis.

  • A. ArnoldA. Papanikolaou
  • Biology, Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2005
Emerging evidence suggests that cyclin D1 might act, predominantly or at least in part, through pathways that do not involve its widely accepted function as a cell cycle regulator.

Cyclin D1 and breast cancer.

The activities of cyclin D1 that drive tumorigenesis.

Cyclin D1: polymorphism, aberrant splicing and cancer risk

It is shown that a specific polymorphism of cyclin D1 (G/A870) and a protein product of a potentially related alternate splicing event (cyclin D 1b) may influence cancer risk and outcome.

The regulation of cyclin D1 degradation: roles in cancer development and the potential for therapeutic invention

Current knowledge on the regulation of cyclin D1 degradation is discussed and novel insights into cyclinD1 degradation are also discussed in the context of ablative therapy.

Requirement for CDK4 kinase function in breast cancer.

Cyclin D1 and D3 associate with the SCF complex and are coordinately elevated in breast cancer

It is suggested that the coordinate increase of D-type cyclins observed in primary breast cancers reflects a defect in their proteolysis and the degradation of cyclin D1 and D3 is deficient in this cell line.

Nuclear cyclin D1: An oncogenic driver in human cancer

Current evidence suggests that nuclear retention of cyclin D1 resulting from altered nuclear trafficking and proteolysis is critical for the manifestation of its oncogenicity.

Specific protection against breast cancers by cyclin D1 ablation

It is reported that cyclin D1-deficient mice are resistant to breast cancers induced by the neu and ras oncogenes, and the results suggest that an anti-cyclIn D1 therapy might be highly specific in treating human breast cancers with activated Neu–Ras pathways.