INIBIDORES DAS TIROSINACINASES NA TERAPÊUTICA FARMACOLÓGICA

Abstract

The discovery of mutations in tyrosine kinases (TKs) involved in the pathogenesis of many diseases, particularly oncological, encouraged the investigation of inhibitors of tyrosine kinases (ITKs) as therapeutic strategies.The aim of this study was to perform a review of the different ITKs available in the national and international markets, their therapeutic indications, and their potential directions in research. It was also a revision of the main ITKs which are currently being evaluated in various stages of clinical trials.We conducted a literature search in the PubMed electronic database using the term “tyrosine kinase inhibitors” and 219 publications were included in the present review, published from August 2011 to July 2012. We also consulted the databases of the Portuguese National Authority of Medicines and Health Products, IP (INFARMED), the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA).Presently there are 14 ITKs approved by FDA. In Portugal there are 13 ITKs with marketing authorization (MA), and bosutinib currently in the authorization phase. There are ITKs approved for the treatment of chronic myeloid leukemia, acute lymphoblastic leukemia, carcinoma of non-small-cell lung cancer, renal cell carcinoma, hepatocellular carcinoma, breast cancer, gastrointestinal stromal tumor, pancreatic neuroendocrine carcinoma, thyroid carcinoma, myelofibrosis and soft tissue sarcomas. ITKs are under investigation for other potential indications such as autoimmune diseases, namely rheumatoid arthritis and psoriasis, among others.Because there is a wide variety of TKs and not all of them are yet studied, more research is needed so that other potential therapeutic targets can be discovered in the future. The TKs are therefore a promising therapeutic target, which makes the ITKs a pharmacological class with great clinical potential.