Targeting non-malignant disorders with tyrosine kinase inhibitors.
Receptor and non-receptor tyrosine kinases are involved in multiple proliferative signalling pathways. Imatinib, one of the first tyrosine kinase inhibitors (TKIs) to be approved, revolutionized the treatment of chronic myelogenous leukaemia, and other TKIs with different spectra of kinase inhibition are used to treat renal cell carcinoma, non-small-cell lung cancer and colon cancer. Studies also support the potential use of TKIs as anti-proliferative agents in non-malignant disorders such as cardiac hypertrophy, and in benign-proliferative disorders including pulmonary hypertension, lung fibrosis, rheumatoid disorders, atherosclerosis, in-stent restenosis and glomerulonephritis. In this Review, we provide an overview of the most recent developments--both experimental as well as clinical--regarding the therapeutic potential of TKIs in non-malignant disorders.
University Hospital Giessen and Marburg, Medical Clinic II/IV/V, Klinikstrasse 36, 35398 Giessen, Germany.
Friedrich
F
Grimminger
Ralph T
RT
Schermuly
Hossein A
HA
Ghofrani
D000818:Animals; D050197:Atherosclerosis / Q000188:drug therapy / Q000201:enzymology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases