Small-molecule inhibitors of the receptor tyrosine kinases: promising tools for targeted cancer therapies

Int J Mol Sci. 2014 Aug 8;15(8):13768-801. doi: 10.3390/ijms150813768.

Abstract

Chemotherapeutic and cytotoxic drugs are widely used in the treatment of cancer. In spite of the improvements in the life quality of patients, their effectiveness is compromised by several disadvantages. This represents a demand for developing new effective strategies with focusing on tumor cells and minimum side effects. Targeted cancer therapies and personalized medicine have been defined as a new type of emerging treatments. Small molecule inhibitors (SMIs) are among the most effective drugs for targeted cancer therapy. The growing number of approved SMIs of receptor tyrosine kinases (RTKs) i.e., tyrosine kinase inhibitors (TKIs) in the clinical oncology imply the increasing attention and application of these therapeutic tools. Most of the current approved RTK-TKIs in preclinical and clinical settings are multi-targeted inhibitors with several side effects. Only a few specific/selective RTK-TKIs have been developed for the treatment of cancer patients. Specific/selective RTK-TKIs have shown less deleterious effects compared to multi-targeted inhibitors. This review intends to highlight the importance of specific/selective TKIs for future development with less side effects and more manageable agents. This article provides an overview of: (1) the characteristics and function of RTKs and TKIs; (2) the recent advances in the improvement of specific/selective RTK-TKIs in preclinical or clinical settings; and (3) emerging RTKs for targeted cancer therapies by TKIs.

Publication types

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

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / therapeutic use
  • Drug Resistance, Neoplasm
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Humans
  • Neoplasms / drug therapy*
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / therapeutic use*
  • Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Receptor Protein-Tyrosine Kinases / metabolism
  • Receptors, Fibroblast Growth Factor / antagonists & inhibitors
  • Receptors, Fibroblast Growth Factor / metabolism
  • Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Receptors, Vascular Endothelial Growth Factor / antagonists & inhibitors
  • Receptors, Vascular Endothelial Growth Factor / metabolism
  • Small Molecule Libraries / chemistry
  • Small Molecule Libraries / therapeutic use
  • fms-Like Tyrosine Kinase 3 / antagonists & inhibitors
  • fms-Like Tyrosine Kinase 3 / metabolism

Substances

  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Receptors, Fibroblast Growth Factor
  • Small Molecule Libraries
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases
  • Receptors, Platelet-Derived Growth Factor
  • Receptors, Vascular Endothelial Growth Factor
  • fms-Like Tyrosine Kinase 3