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

Garth Powis, Alan Kozikowski

Research output: Contribution to journalReview article

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 gowth 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.

Original languageEnglish (US)
Pages (from-to)385-397
Number of pages13
JournalClinical Biochemistry
Volume24
Issue number5
DOIs
StatePublished - Oct 1991

Keywords

  • ether lipid analogues
  • growth factors
  • intracellular Ca
  • intracellular signalling
  • myo-inositol analogues
  • oncogenes
  • protein tyrosine kinases
  • staurosporine

ASJC Scopus subject areas

  • Clinical Biochemistry

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