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

Garth Powis, Alan Kozikowski

Research output: Contribution to journalArticle

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 - 1991
Externally publishedYes

Fingerprint

Inositol
Oncogenes
Intercellular Signaling Peptides and Proteins
Pharmaceutical Preparations
Protein Kinase C
Phosphoinositide Phospholipase C
Antimetabolites
Inositol 1,4,5-Trisphosphate
Staurosporine
Receptor Protein-Tyrosine Kinases
Growth
Alkaloids
Ether
Protein-Tyrosine Kinases
Platelet-Derived Growth Factor Receptors
Cell Proliferation
Cell proliferation
Type C Phospholipases
Phosphatidylinositols
Lipids

Keywords

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

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Growth factor and oncogene signalling pathways as targets for rational anticancer drug development. / Powis, Garth; Kozikowski, Alan.

In: Clinical Biochemistry, Vol. 24, No. 5, 1991, p. 385-397.

Research output: Contribution to journalArticle

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