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Updated: Dec 13, 2025

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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Cyclin D-CDK4/6 functions in cancer

Xueliang Gao1, Gustavo W Leone2, Haizhen Wang3

  • 1Department of Cell and Molecular Pharmacology & Experimental Therapeutics, Medical University of South Carolina, Charleston, SC, United States.

Advances in Cancer Research
|July 30, 2020
PubMed

Insights

Cancer cell cycle regulation involves cyclin-dependent kinases (CDKs). Targeting CDK4/6, crucial for cell cycle progression, offers a promising cancer therapy strategy, with CDK6 showing distinct roles.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • The cell cycle is regulated by cyclin-dependent kinases (CDKs) and cyclins.
  • Dysregulation of cyclin-CDK complexes is a common feature in cancer development.
  • D-type cyclins with CDK4/6 are critical for the G1 to S phase transition by regulating the retinoblastoma protein (RB).

Purpose of the Study:

  • To explore the role of the cyclin D-CDK axis in cancer.
  • To investigate the therapeutic potential of CDK4/6 inhibitors in cancer treatment.
  • To differentiate the specific functions of CDK4 and CDK6 in cancer.

Main Methods:

  • Review of existing pre-clinical and clinical data on cyclin D-CDK pathways in cancer.
  • Analysis of studies involving CDK4/6 dual-inhibitors as single agents or in combination therapies.
  • Examination of research on the distinct roles of CDK4 and CDK6 in cancer biology.

Main Results:

  • The cyclin D-CDK axis is implicated in various cancer hallmarks including proliferation, senescence, migration, apoptosis, and angiogenesis.
  • CDK4/6 inhibitors demonstrate significant efficacy in pre-clinical and clinical cancer settings.
  • CDK6 exhibits unique functions distinct from CDK4 in the context of cancer.

Conclusions:

  • Targeting the cyclin D-CDK4/6 pathway is a viable strategy for cancer therapy.
  • CDK4/6 inhibitors show promise as monotherapies or in combination treatments.
  • Selective depletion of individual CDKs, particularly CDK6, may offer novel therapeutic avenues for cancer patients.
Keywords:
AbemaciclibCDK4CDK4/6 inhibitorCDK6CyclinCyclin-dependent kinasesPROTACPalbociclibRBRibociclib

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