The role of receptor tyrosine kinase inhibition in treating gastrointestinal malignancy.
Tyrosine kinase receptors are proteins that transduce the signal from many growth factor and cytokine ligands to produce intracellular responses. As such they can activate multiple signalling cascade pathways and influence cell division, migration and survival. Many show upregulation in certain malignancies, including those of the gastrointestinal tract, and are thought to play key roles in carcinogenesis. This makes them attractive targets for drug therapy and in recent years many inhibitors have been developed. This review discusses the current situation regarding the development of inhibitors with particular reference to the erbB family, the insulin-like growth factor receptor, the Met receptor, the receptor for vascular endothelial growth factor and the Kit receptor. The evidence will be related back to cancers of the gut lumen. Clinical effectiveness in this area seems to lie in using a combinatorial approach that inhibits multiple key signalling points, and the reasons for this will be discussed.
Anderson
M R
MR
Department of Medical Sciences, University of Birmingham, Vincent Drive, Edgbaston, Birmingham, B15 2TH, UK. M.R.Anderson@bham.ac.uk
Jankowski
J A Z
JA
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000502:physiology*; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D004791:Enzyme Inhibitors; D017978:Receptors, Growth Factor; D020794:Receptor Protein-Tyrosine Kinases