From the Guidelines
Cyclin D1 overexpression is a diagnostic marker for mantle cell lymphoma, and its detection is essential for distinguishing it from other lymphomas, as stated in the most recent and highest quality study 1.
Importance of Cyclin D1 in Cancer Diagnosis
Cyclin D1 is a protein that plays a crucial role in regulating cell cycle progression, specifically controlling the transition from G1 to S phase. It functions by binding to and activating cyclin-dependent kinases (CDK4 and CDK6), which then phosphorylate the retinoblastoma protein (Rb), allowing cells to advance through the cell cycle and proliferate. Overexpression of cyclin D1 is commonly found in various cancers, particularly in mantle cell lymphoma where the CCND1 gene (which encodes cyclin D1) is translocated to the immunoglobulin heavy chain locus, resulting in its constitutive expression. This translocation, designated as t(11;14), serves as a diagnostic marker for mantle cell lymphoma.
Clinical Practice and Cyclin D1
In clinical practice, immunohistochemical staining for cyclin D1 is routinely used in diagnosing mantle cell lymphoma and distinguishing it from other lymphomas, as recommended by the ESMO clinical practice guidelines 1. Understanding cyclin D1's role in cell cycle regulation has led to the development of CDK4/6 inhibitors like palbociclib, ribociclib, and abemaciclib, which are now used in treating hormone receptor-positive breast cancers. The detection of cyclin D1 overexpression is also useful in other types of cancer, such as breast cancer, esophageal cancer, and head and neck squamous cell carcinomas, contributing to uncontrolled cell proliferation.
Recent Studies and Cyclin D1
Recent studies have further emphasized the importance of cyclin D1 in cancer diagnosis and treatment. For example, a study published in 2020 found that CDK4/6 inhibitors can be effective in treating small-cell carcinoma of the ovary, hypercalcemic type, which is characterized by SMARCA4 loss and cyclin D1 downregulation 1. Another study published in 2017 identified a susceptibility locus for renal cell carcinoma on chromosome region 11q13.3, which is attributed to changes in the regulation of CCND1 (encoding cyclin D1) 1. These studies highlight the ongoing research and development of new treatments targeting cyclin D1 and its related pathways.
Key Points
- Cyclin D1 overexpression is a diagnostic marker for mantle cell lymphoma.
- Immunohistochemical staining for cyclin D1 is routinely used in clinical practice to diagnose mantle cell lymphoma.
- CDK4/6 inhibitors are used to treat hormone receptor-positive breast cancers.
- Recent studies have identified new potential targets for cancer treatment related to cyclin D1 and its pathways.
From the Research
Cyclin D1 Overview
- Cyclin D1 is a protein that plays a crucial role in cell cycle control and is implicated in cancer progression 2, 3, 4, 5.
- Overexpression of Cyclin D1 has been associated with high proliferation rates and increased risk of mortality in women with ER-positive breast cancer 3.
- Cyclin D1 has estrogen receptor-dependent divergent functions in breast cancer migration and stem cell-like activity 4.
Role in Breast Cancer
- Cyclin D1 is involved in the pathogenesis of breast cancer, determining uncontrolled cellular proliferation 5.
- High expression of Cyclin D1 is associated with an increased risk of breast cancer death in ER-positive breast cancer 3.
- Cyclin D1 has a role in tumor-stroma interactions, potentiating most of the cancer hallmarks 5.
CDK4/6 Inhibitors and Cyclin D1
- CDK4/6 inhibitors, such as palbociclib, ribociclib, and abemaciclib, are used to treat breast cancer by interrupting cell cycle progression 6.
- Overexpressed Cyclin D1 and CDK4 proteins can lead to resistance to CDK4/6 inhibitors, which can be reversed by PI3K/mTOR inhibitors 2.
- The choice of CDK4/6 inhibitor for an individual patient can be important, considering their similarities and differences in pharmacokinetics and pharmacodynamics 6.