Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 178, Issue 1, Pages 31-53Publisher
WILEY
DOI: 10.1111/bph.14919
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Funding
- Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) [268555672 - SFB 1213]
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This review focuses on the role of kinases in pulmonary hypertension (PH) and highlights the importance of identifying druggable targets in treating the disease. Clinical considerations such as personalized medicine approaches and the management of adverse side effects are also discussed in this context.
Pulmonary hypertension (PH) is a progressive pulmonary vasculopathy that causes chronic right ventricular pressure overload and often leads to right ventricular failure. Various kinase inhibitors have been studied in the setting of PH and either improved or worsened the disease, highlighting the importance of understanding the specific role of the respective kinases in a spatiotemporal cellular context. In this review, we will summarize the knowledge on the role of kinases in PH and focus on druggable targets for which certain criteria are met: (a) deregulation of the kinase in PH; (b) small-molecule inhibitors are available (e.g. from the oncology field); (c) preclinical studies have shown their efficacy in PH models; and (d) when available, therapeutic exploitation in human PH has been initiated. Along this line, clinical considerations such as personalized medicine approaches to predict therapy response and adverse side events such as cardiotoxicity together with their clinical management are discussed.
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