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 language | English (US) |
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Pages (from-to) | 385-397 |
Number of pages | 13 |
Journal | Clinical Biochemistry |
Volume | 24 |
Issue number | 5 |
DOIs | |
State | Published - Oct 1991 |
Externally published | Yes |
Keywords
- ether lipid analogues
- growth factors
- intracellular Ca
- intracellular signalling
- myo-inositol analogues
- oncogenes
- protein tyrosine kinases
- staurosporine
ASJC Scopus subject areas
- Clinical Biochemistry