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.