An Update on the Clinical Use of CDK4/6 Inhibitors in Breast Cancer

Drugs. 2018 Sep;78(13):1353-1362. doi: 10.1007/s40265-018-0972-9.

Abstract

Deregulated cell division, resulting in aberrant cell proliferation, is one of the key hallmarks of cancer. Cyclin-dependent kinases (CDKs) play a central role in cell cycle progression in cancer, and the clinical development of the CDK4/6 inhibitors palbociclib, ribociclib, and abemaciclib has changed clinical practice in the setting of endocrine-receptor positive breast cancer. Results of pivotal phase II and III trials investigating these CDK4/6 inhibitors in patients with endocrine receptor-positive, advanced breast cancer have demonstrated a significant improvement in progression-free survival, with a safe toxicity profile. No validated biomarkers of sensitivity or resistance exist at the moment. Future development of CDK4/6 inhibitors in breast cancer should focus on the identification of predictive biomarkers, the development of drug combinations to overcome resistance, and the application of CDK4/6 inhibitors to other breast cancer subtypes.

Publication types

  • Review

MeSH terms

  • Aminopyridines / pharmacology
  • Aminopyridines / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Benzimidazoles / pharmacology
  • Benzimidazoles / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 6 / metabolism
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Molecular Targeted Therapy
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Progression-Free Survival
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*
  • Purines / pharmacology
  • Purines / therapeutic use
  • Pyridines / pharmacology
  • Pyridines / therapeutic use

Substances

  • Aminopyridines
  • Antineoplastic Agents
  • Benzimidazoles
  • Piperazines
  • Protein Kinase Inhibitors
  • Purines
  • Pyridines
  • abemaciclib
  • CDK4 protein, human
  • CDK6 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6
  • palbociclib
  • ribociclib