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

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

  • Clin Cancer Res. 2015 Jul 1;21(13):2905-10. doi: 10.1158/1078-0432.CCR-14-0816.
Todd VanArsdale 1 Chris Boshoff 2 Kim T Arndt 3 Robert T Abraham 4
Affiliations

Affiliations

  • 1 Oncology Research Unit, Pfizer Worldwide Research and Development, San Diego, California.
  • 2 Pfizer Oncology, San Diego, California.
  • 3 Oncology Research Unit, Pfizer Worldwide Research and Development, Pearl River, New York.
  • 4 Oncology Research Unit, Pfizer Worldwide Research and Development, San Diego, California. Robert.Abraham@pfizer.com.
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.

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