Cancer pharmacologists focus increasingly on the possibility to interfere with cellular signal transduction pathways in the quest for new chemotherapeutic agents. The mechanisms by which signals are transmitted in the cell involve reversible phos-phorylation of proteins. Protein tyrosine kinases, mitogen-activated kinases and protein kinases C are examples of enzymes which catalyse such processes. All three are pivotal constituents of pathways which regulate cell growth. Protein tyrosine kinases are oncogene products. Therefore drugs which can inhibit them might constitute a valuable addition to the oncologist’s chemotherapeutic armamentarium. Examples of prototypes of such drugs are quercetin, erbstatin and tyrphostins. Mitogen-activated kinases are constituents of the signalling pathway involving Ras, of which mutant forms are expressed in many human tumours. Modulators of protein kinases C such as bryostatin 1 and staurosporine possess cytostatic and cyto-toxic properties. Phase I clinical trials of bryostatin 1 have shown that this type of agent elicits effects at very small doses.

Keywords:
Signal transduction, Chemotherapeutic agents, Protein kinase modulators, Bryostatin 1
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© 1994 S. Karger AG, Basel
1994
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