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Mechanism of tyrosine kinase inhibitor imatinib and imatinib-induced cardiotoxicity in treatment of gastrointestinal stromal tumors: Recent progress
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Abstract:
Imatinib, a tyrosine kinase inhibitor, is one of the major drugs for treating gastrointestinal stromal tumor (GIST). However, some patients suffer severe cardiotoxicity after imatinib treatment, with unclear mechanism. Studies have suggested that the different signal transduction pathways mediated by the endoplasmic reticulum stress play a central role in imatinib-induced cardiactoxicity, and these signal pathways can interact with the mitochondrial signal pathway through c-Abl. Competitive binding of imatinib to the ATP binding site in tyrosine kinase domain cause abnormal myocardial energy metabolism and increase oxidative stress, and the sustained oxidative stress lead to abnormal expression of c-Abl and phosphorylation of PDGFR, meanwhile, c-Abl and PDGFR-mediated signal transduction pathway abnormalities is closely associated with imatinib induced cardiotoxicity.
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Project supported by the Shanghai Leading Academic Discipline Foundation (No. B905)
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