Inhibitors of growth factor receptor kinase-dependent signaling pathways in anticancer chemotherapy--clinical progress.
Aberrant signal transduction plays a major role in the pathophysiology of cancer. Kinases, key enzymes involved in signaling pathways, are attractive targets for chemotherapeutic intervention in the fight against cancer. Many cancers respond to endogenous growth factors or, through autocrine loops, express growth factors and the requisite receptor kinases, resulting in cellular proliferation. Growth factor-induced signaling has also been implicated in the activation of anti-apoptotic cell survival pathways. This review attempts to describe some of the key advances made in the last year towards the design and development of inhibitors of growth factor receptor kinases. Particular emphasis is placed on ATP-competitive, small molecule inhibitors of this important class of enzymes.
Renhowe
Paul A
PA
Chiron Corporation, 4560 Horton Street, Emeryville, CA 94608, USA. paul_renhowe@cc.chiron.com
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D019908:Proto-Oncogene Proteins c-raf / Q000037:antagonists & inhibitors; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D017978:Receptors, Growth Factor / Q000037:antagonists & inhibitors; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors; D040262:Receptors, Vascular Endothelial Growth Factor; D015398:Signal Transduction / Q000187:drug effects*
D000970:Antineoplastic Agents; D017978:Receptors, Growth Factor; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D017479:Receptors, Platelet-Derived Growth Factor; D040262:Receptors, Vascular Endothelial Growth Factor; D019908:Proto-Oncogene Proteins c-raf