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) |
|---|---|
| Pages (from-to) | 385-397 |
| Number of pages | 13 |
| Journal | Clinical Biochemistry |
| Volume | 24 |
| Issue number | 5 |
| DOIs | |
| State | Published - 1991 |
| Externally published | Yes |
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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 journal › Article
}
TY - JOUR
T1 - Growth factor and oncogene signalling pathways as targets for rational anticancer drug development
AU - Powis, Garth
AU - Kozikowski, Alan
PY - 1991
Y1 - 1991
N2 - 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.
AB - 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.
KW - ether lipid analogues
KW - growth factors
KW - intracellular Ca
KW - intracellular signalling
KW - myo-inositol analogues
KW - oncogenes
KW - protein tyrosine kinases
KW - staurosporine
UR - http://www.scopus.com/inward/record.url?scp=0025955684&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0025955684&partnerID=8YFLogxK
U2 - 10.1016/S0009-9120(05)80014-1
DO - 10.1016/S0009-9120(05)80014-1
M3 - Article
C2 - 1760877
AN - SCOPUS:0025955684
VL - 24
SP - 385
EP - 397
JO - Clinical Biochemistry
JF - Clinical Biochemistry
SN - 0009-9120
IS - 5
ER -