Growth factor and oncogene signalling pathways as targets for rational anticancer drug development

Clin Biochem. 1991 Oct;24(5):385-97. doi: 10.1016/s0009-9120(05)80014-1.

Abstract

There is a critical need for new targets, in addition to DNA, for anticancer drug development. A recently discovered target is the intracellular signalling pathways that mediate the actions of growth factors and oncogenes on cell proliferation. Two important pathways, the myo-inositol and protein tyrosine kinase signalling pathways are reviewed. Three classes of compounds that modulate myo-inositol signalling are discussed. These are: 1) the D-3-substituted-3-deoxy-myo-inositol analogues that act as antimetabolites of myo-inositol and show selective growth inhibition of some transformed cells; 2) the alkaloid staurosporine that acts as a potent inhibitor of protein kinase C and of platelet-derived growth factor (PDGF) receptor protein tyrosine kinase activity; 3) the ether lipid analogues that block growth factor signalling at several points by acting as inhibitors of protein kinase C, phosphoinositide specific phospholipase C and inositol(1,4,5)trisphosphate-induced Ca2+ release. It is suggested that inhibition of signalling pathways may explain the growth inhibitory effects of these compounds. Other potential signalling target sites for anticancer drug development are discussed.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Alkaloids / pharmacology
  • Animals
  • Antineoplastic Agents / pharmacology*
  • Drug Design
  • Growth Substances / metabolism*
  • Humans
  • Inositol / analogs & derivatives
  • Inositol / metabolism
  • Lipids / pharmacology
  • Oncogenes / drug effects*
  • Protein-Tyrosine Kinases / metabolism
  • Signal Transduction / drug effects*
  • Staurosporine

Substances

  • Alkaloids
  • Antineoplastic Agents
  • Growth Substances
  • Lipids
  • Inositol
  • Protein-Tyrosine Kinases
  • Staurosporine