A clinical evaluation of treatments that target cell cycle machinery in breast cancer

Expert Opin Pharmacother. 2019 Dec;20(18):2305-2315. doi: 10.1080/14656566.2019.1672659. Epub 2019 Oct 14.

Abstract

Introduction: The dysregulation of cell cycle control can lead to cancer development. In breast cancer, cyclin D, CDK 4,6 and the retinoblastoma protein play a central role in the control of cell proliferation, in crosstalk with the estrogen receptor and Her2 pathways. Although the mechanisms by which the CDK4/6 complex is involved in the control of cell growth in triple negative breast cancer (TNBC) are still unclear, some TNBCs might be sensitive to CDK4/6 inhibitors.Areas covered: The authors provide an overview of the treatments that target cell cycle machinery in breast cancer and provide their perspectives for the future.Expert opinion: CDK 4/6 inhibitors are active drugs in HR+ MBC, but some unresolved issues remain. We need to identify biomarkers of response. Moreover, we need to determine the optimal timing for the incorporation of CDK 4/6 inhibitors in the current treatment algorithm. In the Her2 positive subtype, the triple combination of anti Her2 therapies with CDK4/6 inhibitors and endocrine therapy seems to be a promising chemotherapy free approach. Efforts must still be made for the treatment of the TNBC subtype, even though new CDK 4/6 combinations are emerging as promising approaches to selected patients.

Keywords: CDK4/6 inhibitors; HR+ breast cancer; Her2 positive breast cancer; cell cycle; targeted treatment; triple negative breast cancer.

Publication types

  • Review

MeSH terms

  • Breast Neoplasms / drug therapy*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors
  • Female
  • Humans
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptor, ErbB-2 / metabolism
  • Receptors, Estrogen / metabolism
  • Triple Negative Breast Neoplasms / drug therapy

Substances

  • Protein Kinase Inhibitors
  • Receptors, Estrogen
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6