Cell cycle proteins as promising targets in cancer therapy

Nat Rev Cancer. 2017 Jan 27;17(2):93-115. doi: 10.1038/nrc.2016.138.

Abstract

Cancer is characterized by uncontrolled tumour cell proliferation resulting from aberrant activity of various cell cycle proteins. Therefore, cell cycle regulators are considered attractive targets in cancer therapy. Intriguingly, animal models demonstrate that some of these proteins are not essential for proliferation of non-transformed cells and development of most tissues. By contrast, many cancers are uniquely dependent on these proteins and hence are selectively sensitive to their inhibition. After decades of research on the physiological functions of cell cycle proteins and their relevance for cancer, this knowledge recently translated into the first approved cancer therapeutic targeting of a direct regulator of the cell cycle. In this Review, we focus on proteins that directly regulate cell cycle progression (such as cyclin-dependent kinases (CDKs)), as well as checkpoint kinases, Aurora kinases and Polo-like kinases (PLKs). We discuss the role of cell cycle proteins in cancer, the rationale for targeting them in cancer treatment and results of clinical trials, as well as the future therapeutic potential of various cell cycle inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Aurora Kinase A / antagonists & inhibitors
  • Aurora Kinase A / physiology
  • Cell Cycle Proteins / antagonists & inhibitors*
  • Cell Cycle Proteins / physiology
  • Checkpoint Kinase 1 / antagonists & inhibitors
  • Checkpoint Kinase 1 / physiology
  • Clinical Trials as Topic
  • Cyclin-Dependent Kinase 2 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 2 / physiology
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 4 / physiology
  • Cyclin-Dependent Kinase 6 / antagonists & inhibitors
  • Cyclin-Dependent Kinase 6 / physiology
  • Humans
  • Neoplasms / drug therapy*
  • Nuclear Proteins / antagonists & inhibitors
  • Nuclear Proteins / physiology
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / physiology
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Protein-Tyrosine Kinases / physiology
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / physiology
  • Signal Transduction

Substances

  • Cell Cycle Proteins
  • Nuclear Proteins
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • WEE1 protein, human
  • Aurora Kinase A
  • Checkpoint Kinase 1
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • Cyclin-Dependent Kinase 2
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase 6