From the Guidelines
Cyclin D1 overexpression is a key diagnostic marker for mantle cell lymphoma, and its detection is mandatory for diagnosis, as stated in the ESMO clinical practice guidelines 1.
Importance of Cyclin D1 in Cancer Biology
Cyclin D1 is a crucial cell cycle regulatory protein that controls the transition from G1 to S phase during cell division. It functions by binding to and activating cyclin-dependent kinases (CDK4 and CDK6), which then phosphorylate the retinoblastoma protein (Rb), allowing cells to progress through the cell cycle. Overexpression of cyclin D1 is commonly found in various cancers, particularly in mantle cell lymphoma where the t(11;14) translocation places the cyclin D1 gene under the control of the immunoglobulin heavy chain promoter, leading to its constitutive expression.
Diagnostic and Therapeutic Implications
In clinical practice, cyclin D1 is an important diagnostic marker for mantle cell lymphoma, distinguishing it from other B-cell lymphomas. The detection of cyclin D1 overexpression is essential for the diagnosis of mantle cell lymphoma, and it is recommended that a surgical specimen, preferably a lymph node biopsy, be used for diagnosis 1. Additionally, cyclin D1 amplification or overexpression is observed in breast, esophageal, bladder, and lung cancers, making it a potential therapeutic target. CDK4/6 inhibitors like palbociclib, ribociclib, and abemaciclib, which block cyclin D1 activity, have been developed and approved for treating hormone receptor-positive, HER2-negative advanced breast cancer, demonstrating the clinical relevance of understanding cyclin D1's role in cancer biology.
Cyclin D1 and Cancer Risk
Genetic factors also contribute to cancer risk, and investigations into familial cancers have uncovered mutations in at least 11 genes, some of which have also been implicated in sporadic cancer development 1. Genome-wide association studies (GWAS) of cancer have identified susceptibility loci, including one on chromosome region 11q13.3, which seems to be attributable to changes in the regulation of CCND1 (encoding cyclin D1) 1.
Key Points
- Cyclin D1 overexpression is a key diagnostic marker for mantle cell lymphoma.
- Detection of cyclin D1 overexpression is essential for diagnosis.
- Cyclin D1 is a potential therapeutic target for various cancers, including breast, esophageal, bladder, and lung cancers.
- CDK4/6 inhibitors have been developed and approved for treating hormone receptor-positive, HER2-negative advanced breast cancer.
From the Research
Cyclin D1 Overview
- Cyclin D1 is a crucial regulator of the cell cycle, and its overexpression is associated with cancer development, particularly in breast cancer 2, 3, 4.
- The CCDN1 gene, which encodes Cyclin D1, is amplified in various tumor types, making it a negative prognostic marker 2.
- Cyclin D1 plays a central role in cell cycle control, adhesion, invasion, and tumor-stroma interactions, contributing to cancer hallmarks 2, 4.
Role in Cancer
- Cyclin D1 overexpression is found in more than 50% of human breast cancers and can cause mammary cancer in transgenic mice 3.
- Dysregulation of Cyclin D1 gene expression or function contributes to the loss of normal cell cycle control during tumorigenesis 3, 4.
- Cyclin D1 conducts additional specific functions, such as regulating gene expression, promoting cellular migration, and promoting chromosomal instability 3.
Therapeutic Options
- CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, have been approved for use in combination with endocrine therapy for the treatment of hormone receptor-positive, HER2-negative breast cancer 5, 6.
- These inhibitors trigger cell cycle arrest in Rb protein (pRb)-competent cells and have delivered promising results of efficacy and manageable safety profiles 5, 6.
- Ongoing clinical trials are investigating the use of CDK4/6 inhibitors in combination with endocrine therapy in early breast cancer and in combination with other agents in advanced settings 6.