CDK4, CDK6/cyclin-D1 Complex Inhibition and Radiotherapy for Cancer Control: A Role for Autophagy

Int J Mol Sci. 2021 Aug 4;22(16):8391. doi: 10.3390/ijms22168391.

Abstract

The expanding clinical application of CDK4- and CDK6-inhibiting drugs in the managements of breast cancer has raised a great interest in testing these drugs in other neoplasms. The potential of combining these drugs with other therapeutic approaches seems to be an interesting work-ground to explore. Even though a potential integration of CDK4 and CDK6 inhibitors with radiotherapy (RT) has been hypothesized, this kind of approach has not been sufficiently pursued, neither in preclinical nor in clinical studies. Similarly, the most recent discoveries focusing on autophagy, as a possible target pathway able to enhance the antitumor efficacy of CDK4 and CDK6 inhibitors is promising but needs more investigations. The aim of this review is to discuss the recent literature on the field in order to infer a rational combination strategy including cyclin-D1/CDK4-CDK6 inhibitors, RT, and/or other anticancer agents targeting G1-S phase cell cycle transition.

Keywords: autophagy; cyclin inhibitors; radiotherapy.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Autophagy / drug effects
  • Autophagy / radiation effects
  • Cell Cycle / drug effects
  • Cell Cycle / radiation effects
  • Chemoradiotherapy
  • Cyclin D1 / antagonists & inhibitors
  • Cyclin D1 / metabolism
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 6 / metabolism
  • Humans
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Neoplasms / radiotherapy*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Cyclin D1
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6