Modulators of signal transduction as cancer chemotherapeutic agents--novel mechanisms and toxicities.
The recent explosion of knowledge of the molecular basis of regulation of growth and differentiation has engendered the search for novel anticancer drugs which act via interference with cellular signal transduction pathways. Among the agents which are under investigation are modulators of protein kinases, for example quercetin and bryostatin 1. Both compounds have undergone phase 1 clinical evaluation. The major dose-limiting toxicities of quercetin and bryostatin are nephrotoxicity and myalgia, respectively. Novel analogs of the microbial product staurosporine, a potent kinase inhibitor, possess intriguing specificities for different kinases.
Gescher
A
A
MRC Toxicology Unit, University of Leicester, UK.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D011493:Protein Kinase C / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D018631:ras Proteins / Q000502:physiology
D000970:Antineoplastic Agents; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D018631:ras Proteins