Targeting tyrosine kinases in cancer: the second wave

Science. 2006 May 26;312(5777):1175-8. doi: 10.1126/science.1125951.

Abstract

One of the most exciting developments in cancer research in recent years has been the clinical validation of molecularly targeted drugs that inhibit the action of pathogenic tyrosine kinases. Treatment of appropriately selected patients with these drugs can alter the natural history of their disease and improve survival. The clinical validation of these "first-generation" tyrosine kinase inhibitors has been the prelude to a second wave of advances in molecular targeting that is expected to further change the way we classify and treat cancer. Efforts are now being directed at identifying the tumor subtypes and patients who will benefit the most from these drugs. In addition, new compounds that circumvent acquired resistance to the first-generation tyrosine kinase inhibitors are being tested in patients with refractory disease. Agents directed against new molecular targets are also being explored.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / therapeutic use*
  • Benzamides
  • Drug Resistance, Neoplasm
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / metabolism
  • Fusion Proteins, bcr-abl / antagonists & inhibitors
  • Fusion Proteins, bcr-abl / metabolism
  • Humans
  • Imatinib Mesylate
  • Mutation
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Piperazines / pharmacology
  • Piperazines / therapeutic use
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors*
  • Protein-Tyrosine Kinases / genetics
  • Proto-Oncogene Proteins c-kit / metabolism
  • Pyrimidines / pharmacology
  • Pyrimidines / therapeutic use
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / metabolism
  • Receptors, Platelet-Derived Growth Factor / antagonists & inhibitors
  • Receptors, Platelet-Derived Growth Factor / metabolism
  • Trastuzumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Imatinib Mesylate
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins c-kit
  • Receptor, ErbB-2
  • Receptors, Platelet-Derived Growth Factor
  • Fusion Proteins, bcr-abl
  • Trastuzumab