Cyclin-Dependent Kinases (CDKs)
Definition
- CDKs are a family of serine/threonine kinases that regulate cell cycle progression and transcription.
- Function by forming complexes with cyclins to drive transition through specific phases of the cell cycle (G1, S, G2, M).
| CDK | Phase / Role | Relevance in Cancer |
|---|---|---|
| CDK4/6 | G1 → S transition; forms complex with cyclin D | Frequently overactive in ER+ breast cancer → uncontrolled proliferation |
| CDK1, 2 | G2/M and S phase transitions | Dysregulation contributes to various malignancies |
| CDK7, 9 | Transcriptional regulation via RNA Pol II | Targeted in certain leukemias and solid tumors in trials |
CDK Inhibitors (Targeted Therapy)
- CDK4/6 inhibitors (main clinically used class in oncology):
- Palbociclib (Ibrance)
- Ribociclib (Kisqali)
- Abemaciclib (Verzenio)
- Indications:
- HR-positive, HER2-negative advanced/metastatic breast cancer (often with endocrine therapy).
- Mechanism: Inhibit CDK4/6 → prevent phosphorylation of Rb protein → G1 cell cycle arrest → slows tumor proliferation.
Key Toxicities of CDK4/6 Inhibitors
| Drug | Major Toxicities / Monitoring |
|---|---|
| Palbociclib | Neutropenia, leukopenia, fatigue, infections; monitor CBC |
| Ribociclib | Neutropenia, QT prolongation, hepatotoxicity; monitor CBC, LFTs, ECG |
| Abemaciclib | Diarrhea (more frequent), neutropenia, fatigue; monitor CBC and electrolytes |
Pharmacist Pearls
- CYP3A4 metabolism → watch for drug–drug interactions with strong inhibitors/inducers.
- Usually given in combination with endocrine therapy (letrozole, fulvestrant).
- Dose adjustments may be needed for toxicity or drug interactions.
- Educate patients on infection risk, diarrhea management, and monitoring schedules.
Summary:
- CDKs regulate cell cycle progression.
- CDK4/6 inhibitors are approved targeted therapies for HR+/HER2- breast cancer.
- Monitoring focuses on hematologic toxicity, liver function, and cardiac safety (for ribociclib).