Cyclins and cyclin-dependent kinases: from biology to tumorigenesis and therapeutic opportunities

J Cancer Res Clin Oncol. 2023 Apr;149(4):1585-1606. doi: 10.1007/s00432-022-04135-6. Epub 2022 Jul 4.

Abstract

The discussion on cell proliferation cannot be continued without taking a look at the cell cycle regulatory machinery. Cyclin-dependent kinases (CDKs), cyclins, and CDK inhibitors (CKIs) are valuable members of this system and their equilibrium guarantees the proper progression of the cell cycle. As expected, any dysregulation in the expression or function of these components can provide a platform for excessive cell proliferation leading to tumorigenesis. The high frequency of CDK abnormalities in human cancers, together with their druggable structure has raised the possibility that perhaps designing a series of inhibitors targeting CDKs might be advantageous for restricting the survival of tumor cells; however, their application has faced a serious concern, since these groups of serine-threonine kinases possess non-canonical functions as well. In the present review, we aimed to take a look at the biology of CDKs and then magnify their contribution to tumorigenesis. Then, by arguing the bright and dark aspects of CDK inhibition in the treatment of human cancers, we intend to reach a consensus on the application of these inhibitors in clinical settings.

Keywords: CDK; CDK inhibitors; Cancer; Cell cycle; Cyclin; Cyclin-dependent kinases.

Publication types

  • Review

MeSH terms

  • Biology
  • Cell Cycle / physiology
  • Cell Transformation, Neoplastic
  • Cyclin-Dependent Kinases*
  • Cyclins / metabolism
  • Cyclins / therapeutic use
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / metabolism

Substances

  • Cyclin-Dependent Kinases
  • Cyclins