Therapeutic opportunities to control tumor cell cycles

Clin Transl Oncol. 2006 Jun;8(6):399-408. doi: 10.1007/s12094-006-0193-7.

Abstract

Tumor cell proliferation is frequently associated to genetic or epigenetic alterations in key cell cycle regulators. Most human tumors deregulate this pathway to sustain proliferation with independence of external mitogenic factors. In addition, the alteration of cell cycle proteins may confer genomic instability that results in additional mutations in these tumor cells. The frequent alteration of the cell cycle in tumor cells has launched the identification for critical cell cycle regulators as anticancer targets. The inhibition of some cell cycle kinases such as cyclin-dependent kinases (CDKs) or the Aurora and Polo mitotic kinases is currently under study in several preclinical and clinical trials. Similarly, the clinical success of microtubule poisons such as taxol has promoted new applied research in mitosis regulation. Recent investigations have suggested new targets of interest including additional kinases, phosphatases and other mitotic regulators such as microtubule motor proteins (kinesins). Current research in this area will undoubtedly result in new and improved targeted therapies for cancer treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aurora Kinases
  • Cell Cycle / drug effects*
  • Cell Cycle / genetics
  • Cell Cycle / physiology
  • Cell Cycle Proteins / antagonists & inhibitors*
  • Cell Cycle Proteins / physiology
  • Chromosome Segregation / drug effects
  • Chromosome Segregation / physiology
  • Cyclin-Dependent Kinase Inhibitor Proteins / physiology
  • Cyclin-Dependent Kinases / antagonists & inhibitors
  • Cyclin-Dependent Kinases / physiology
  • DNA Damage
  • DNA Replication / drug effects
  • Drug Design
  • Forecasting
  • G1 Phase / drug effects
  • Genes, cdc
  • Humans
  • Mice
  • Models, Biological
  • Molecular Motor Proteins
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / physiology
  • Neoplasms / drug therapy*
  • Neoplasms / genetics
  • Neoplasms / physiopathology
  • Phosphoprotein Phosphatases / physiology
  • Phosphorylation / drug effects
  • Protein Processing, Post-Translational / drug effects
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / physiology
  • Proto-Oncogene Proteins / antagonists & inhibitors
  • Proto-Oncogene Proteins / physiology
  • Signal Transduction / drug effects
  • Spindle Apparatus / drug effects*

Substances

  • Cell Cycle Proteins
  • Cyclin-Dependent Kinase Inhibitor Proteins
  • Molecular Motor Proteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Aurora Kinases
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • Cyclin-Dependent Kinases
  • Phosphoprotein Phosphatases