Molecular Pathways: Targeting the Cyclin D–CDK4/6 Axis for Cancer Treatment
| Autor: | Robert T. Abraham, Chris Boshoff, Kim Arndt, Todd VanArsdale |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Cancer Research
Cyclin D Antineoplastic Agents Palbociclib Cyclin-dependent kinase Neoplasms medicine Animals Humans Molecular Targeted Therapy Protein Kinase Inhibitors neoplasms Cyclin D/Cdk4 biology Cyclin-dependent kinase 4 Retinoblastoma Cyclin-Dependent Kinase 4 Cyclin-Dependent Kinase 6 medicine.disease Cell biology Oncology Cancer cell biology.protein Cyclin-dependent kinase 6 biological phenomena cell phenomena and immunity Signal Transduction |
| Zdroj: | Clinical Cancer Research. 21:2905-2910 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-14-0816 |
| Popis: | Cancer cells bypass normal controls over mitotic cell-cycle progression to achieve a deregulated state of proliferation. The retinoblastoma tumor suppressor protein (pRb) governs a key cell-cycle checkpoint that normally prevents G1-phase cells from entering S-phase in the absence of appropriate mitogenic signals. Cancer cells frequently overcome pRb-dependent growth suppression via constitutive phosphorylation and inactivation of pRb function by cyclin-dependent kinase (CDK) 4 or CDK6 partnered with D-type cyclins. Three selective CDK4/6 inhibitors, palbociclib (Ibrance; Pfizer), ribociclib (Novartis), and abemaciclib (Lilly), are in various stages of development in a variety of pRb-positive tumor types, including breast cancer, melanoma, liposarcoma, and non–small cell lung cancer. The emerging, positive clinical data obtained to date finally validate the two decades-old hypothesis that the cyclin D–CDK4/6 pathway is a rational target for cancer therapy. Clin Cancer Res; 21(13); 2905–10. ©2015 AACR. |
| Databáze: | OpenAIRE |
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