HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Molecular Pathways: Targeting the Cyclin D-CDK4/6 Axis for Cancer Treatment.

Abstract
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.
AuthorsTodd VanArsdale, Chris Boshoff, Kim T Arndt, Robert T Abraham
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 21 Issue 13 Pg. 2905-10 (Jul 01 2015) ISSN: 1557-3265 [Electronic] United States
PMID25941111 (Publication Type: Journal Article, Review)
Copyright©2015 American Association for Cancer Research.
Chemical References
  • Antineoplastic Agents
  • Cyclin D
  • Protein Kinase Inhibitors
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
Topics
  • Animals
  • Antineoplastic Agents (pharmacology, therapeutic use)
  • Cyclin D (antagonists & inhibitors, metabolism)
  • Cyclin-Dependent Kinase 4 (antagonists & inhibitors, metabolism)
  • Cyclin-Dependent Kinase 6 (antagonists & inhibitors, metabolism)
  • Humans
  • Molecular Targeted Therapy
  • Neoplasms (drug therapy, metabolism)
  • Protein Kinase Inhibitors (pharmacology, therapeutic use)
  • Signal Transduction

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: