Imatinib does not induce cardiotoxicity at clinically relevant concentrations in preclinical studies

Wolf, Armin; Couttet, Philippe; Dong, Min; Grenet, Olivier; Heron, Marcia I.; Junker, Ursula; Laengle, U W; David, Lior; Marrer, Estelle; Nussher, Anja; Persohn, Elke; Philippe, François; Riviere, Gilles-Jacques; Roth, Daniel; Trendelenburg, Christian; Tsao, Jeffrey; Roman, Danielle

doi:10.1016/j.leukres.2010.01.004

Cited by 64 publications

(50 citation statements)

References 28 publications

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“…Wolf et al [32] have also reported myocyte necrosis in rats treated with higher doses of Imb for 28 d (120 or 200 mg/kg).…”

Section: Discussionmentioning

confidence: 90%

“…In addition, Wolf et al [32] found that cardiac alterations (necrosis) in rats occurred only at high nonclinically relevant doses. A dose-dependent, short-lasting decrease in arterial blood pressure (BP) was observed immediately after single dose administration in rats but no electrocardiogram (ECG) changes were observed.…”

Section: Discussionmentioning

confidence: 99%

“…The measurement of serum cardiac troponins (cTnI and cTnT) are the gold standard for diagnosis of acute myocardial events in man and have gained increasing recognition as a new tool for the assessment of cardiotoxicity in safety studies [14].Also, Wolf et al [32] also reported that levels of cTnI increased in some Imb-treated rats. In this instance, increases in heart rate and contractility preceded necrotic degeneration of the myocytes.…”

Section: Discussionmentioning

confidence: 99%

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Study of Imatinib Cardiotoxicity In Adult Male Rabbits

Hassan¹,

Yousef²

2013

IOSR-JESTFT

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“…Wolf et al [32] have also reported myocyte necrosis in rats treated with higher doses of Imb for 28 d (120 or 200 mg/kg).…”

Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Study of Imatinib Cardiotoxicity In Adult Male Rabbits

Hassan¹,

Yousef²

2013

IOSR-JESTFT

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show abstract

“…11) However, one of later studies presented evidence that IM-induced apoptosis may not be related to the inhibition of tyrosine kinase by the drug, 13) which suggested that some unknown mechanisms may be involved. Recently, one of our studies revealed that IM induced apoptosis via inhibition of HERG expression in CML, which may contribute to its clinical efficacy.…”

Section: Discussionmentioning

confidence: 99%

“…10,11) In vitro, IM induced significant cell apoptosis and death in isolated cardiomyocytes. 12,13) Additionally, IM targets cellular mechanisms other than tyrosine kinase, including voltage-gated potassium and calcium channels. [14][15][16][17] Furthermore, we have recently shown that IM significantly reduces HERG currents as well as its expression in CML.…”

mentioning

confidence: 99%

Blocking of the Human Ether-à-go-go-Related Gene Channel by Imatinib Mesylate

Zhao

et al. 2013

Biological & Pharmaceutical Bulletin

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Imatinib mesylate (IM), a widely prescribed powerful tyrosine kinase inhibitor, has been associated with increased risk of heart failure and is known to induce cell apoptosis and death in isolated cardiomyocytes. In addition to acquired long QT syndrome, pharmacological inhibition of human ether-à-go-go-related gene (HERG) channel has been reported to involve in apoptosis. The present study was undertaken to characterize the biophysical properties of IM on HERG and the molecular determinants of HERG blockade using mutant channels (

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Practical management of patients with chronic myeloid leukemia

Cervantes¹,

Mauro²

2011

Cancer

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Although imatinib has been used as frontline therapy for chronic myeloid leukemia (CML) for nearly a decade, current debate is focused on the incorporation of newer tyrosine kinase inhibitors (TKIs) at diagnosis in light of recent US Food and Drug Administration approval of nilotinib and dasatinib for initial therapy in chronic-phase CML. Articles were identified through a PubMed search and a review of abstracts from relevant hematology congresses. Additional information was provided from the authors' libraries and expertise. With several therapies now available, it is crucial to carefully define and monitor response in patients with CML to determine whether their treatment is appropriate and is providing an optimal outcome. Different patterns of response to TKI treatment have been recognized, ranging from best-case scenarios of rapid and unwavering response to difficult situations of intolerance and resistance, either primary or secondary. Patients who develop resistance to imatinib are advised to switch to second-generation TKIs. Although specific mutations in the breakpoint cluster region-v-abl Abelson murine leukemia viral oncogene (BCR-ABL) kinase domain may guide treatment selection in such scenarios, the choice is driven by other factors in the majority of patients, including the toxicity profiles of the newer TKIs as well as a patient's comorbidities.

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Imatinib does not induce cardiotoxicity at clinically relevant concentrations in preclinical studies

Cited by 64 publications

References 28 publications

Study of Imatinib Cardiotoxicity In Adult Male Rabbits

Study of Imatinib Cardiotoxicity In Adult Male Rabbits

Blocking of the Human Ether-à-go-go-Related Gene Channel by Imatinib Mesylate

Practical management of patients with chronic myeloid leukemia

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