Investigating the association between ALK Receptor Tyrosine Kinase inhibitors and pulmonary arterial hypertension: a disproportionality analysis from the WHO pharmacovigilance database

2021 ◽  
pp. 2101576
Author(s):  
Charles Khouri ◽  
Alex Hlavaty ◽  
Matthieu Roustit ◽  
Jean-Luc Cracowski ◽  
Marie-Camille Chaumais ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Tyrosine Kinase ◽  
Arterial Hypertension ◽  
Tyrosine Kinase Inhibitors ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Disproportionality Analysis ◽  
Pharmacovigilance Database ◽  
Pulmonary Arterial ◽  
Receptor Tyrosine Kinase Inhibitors

Pulmonary complications of Bcr-Abl tyrosine kinase inhibitors

2020 ◽  
Vol 56 (4) ◽  
pp. 2000279 ◽  
Author(s):  
Jason Weatherald ◽  
Louise Bondeelle ◽  
Marie-Camille Chaumais ◽  
Christophe Guignabert ◽  
Laurent Savale ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Tyrosine Kinase ◽  
Arterial Hypertension ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Chronic Myelogenous Leukaemia ◽  
Pulmonary Complications ◽  
Myelogenous Leukaemia ◽  
Dependent Manner ◽  
Pulmonary Arterial

Tyrosine kinase inhibitors (TKIs) targeting the Bcr-Abl oncoprotein revolutionised the treatment of chronic myelogenous leukaemia. Following the success of imatinib, second- and third-generation molecules were developed. Different profiles of kinase inhibition and off-target effects vary between TKIs, which leads to a broad spectrum of potential toxicities.Pulmonary complications are most frequently observed with dasatinib but all other Bcr-Abl TKIs have been implicated. Pleural effusions are the most frequent pulmonary complication of TKIs, usually associated with dasatinib and bosutinib. Pulmonary arterial hypertension is an uncommon but serious complication of dasatinib, which is often reversible upon discontinuation. Bosutinib and ponatinib have also been associated with pulmonary arterial hypertension, while imatinib has not. Rarely, interstitial lung disease has been associated with TKIs, predominantly with imatinib.Mechanistically, dasatinib affects maintenance of normal pulmonary endothelial integrity by generating mitochondrial oxidative stress, inducing endothelial apoptosis and impairing vascular permeability in a dose-dependent manner. The mechanisms underlying other TKI-related complications are largely unknown. Awareness and early diagnosis of the pulmonary complications of Bcr-Abl TKIs is essential given their seriousness, potential reversibility, and impact on future treatment options for the underlying chronic myelogenous leukaemia.

Tyrosine Kinase Inhibitors in Pulmonary Arterial Hypertension: A Double-Edge Sword?

2013 ◽  
Vol 34 (05) ◽  
pp. 714-724 ◽  
Author(s):  
Laurent Godinas ◽  
Christophe Guignabert ◽  
Andrei Seferian ◽  
Frederic Perros ◽  
Emmanuel Bergot ◽  
...  
Keyword(s):  
Pulmonary Arterial Hypertension ◽  
Tyrosine Kinase ◽  
Arterial Hypertension ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Double Edge ◽  
Double Edge Sword ◽  
Pulmonary Arterial

Novel azulene-based derivatives as potent multi-receptor tyrosine kinase inhibitors

2010 ◽  
Vol 20 (20) ◽  
pp. 6129-6132 ◽  
Author(s):  
Chih-Hung Chen ◽  
On Lee ◽  
Chung-Niang Yao ◽  
Meng-Yun Chuang ◽  
Yow-Lone Chang ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Tyrosine Kinase Inhibitors ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitors ◽  
Receptor Tyrosine Kinase Inhibitors
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