Signal-transduction therapy. A novel approach to disease management.
In the past decade it has become apparent that many diseases result from aberrations in signaling pathways. These include proliferative diseases such as cancers, atherosclerosis and psoriasis and inflammatory conditions such as sepsis, rheumatoid arthritis and tissue rejection. These findings refocused the research of the medical community to seek new modalities for disease management which essentially consist of designing drugs which intercept cell signaling. In this review, the emerging success in using tyrosine kinase blockers and other signal interceptors, such as protein kinase C blockers, Ras blockers, Ca2+ signaling inhibitors and estrogen antagonists which inhibit growth of cancer cells in vitro and in vivo, will be discussed. These signal interceptors, especially tyrosine-kinase blockers, are also able to block inflammatory responses and the proliferation of vascular smooth muscle cells and psoriatic keratinocytes. The utility of signal interceptors in analyzing signal-transduction pathways is also discussed.
Levitzki
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Department of Biological Chemistry, Hebrew University of Jerusalem, Israel.
D001161:Arteriosclerosis / Q000628:therapy; D002118:Calcium / Q000378:metabolism; D003131:Combined Modality Therapy; D006084:Graft Rejection / Q000628:therapy; D006801:Humans; D007165:Immunosuppression Therapy; D007527:Isoenzymes / Q000378:metabolism; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D010739:Phospholipase D / Q000037:antagonists & inhibitors; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011565:Psoriasis / Q000628:therapy; D011987:Receptors, Steroid / Q000037:antagonists & inhibitors; D012772:Shock, Septic / Q000628:therapy; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors; D018631:ras Proteins / Q000037:antagonists & inhibitors
D007527:Isoenzymes; D011987:Receptors, Steroid; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases; D010739:Phospholipase D; D018631:ras Proteins; D002118:Calcium