Intracellular Signaling Pathways Mediating Tyrosine Kinase Inhibitor Cardiotoxicity

Scott, Shane S.; Greenlee, Ashley N.; Matzko, Anna; Stein, Matthew D.; Naughton, Michael T.; Zaramo, Taborah Z.; Schwendeman, Ethan; Mohammad, Somayya J.; Diallo, Mamadou; Revan, Rohith; Shimmin, Gabriel; Tarun, Shwetabh; Ferrall, Joel; Ho, Thai H.; Smith, Sakima A.

doi:10.1016/j.hfc.2022.02.003

Cited by 9 publications

(3 citation statements)

References 118 publications

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“…In addition to PDGFR-β signaling inhibition, there was another mechanism may also contribute to cardiac failure. The interaction between endothelial cells(ECs) and cardiomyocytes was essential for maintaining cardiac homeostasis and angiogenesis [40]. VEGFR-2 on cardiac ECs inhibited by TKIs initiated downstream signaling changes, leading to cardiomyocyte apoptosis, hypertrophy, and finally resulted in cardiac failure [41].…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular toxicities following the use of tyrosine kinase inhibitors in Hepatocellular Cancer Patients: A Retrospective, Pharmacovigilance Study

Lai

Wan

Jiao

et al. 2023

Preprint

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Aims: With the extensive use of tyrosine kinases inhibitors(TKIs) in hepatocellular cancer, cardiac adverse events(AEs) emerged in recent years. This study explored the cardiac AEs of TKIs through the Food and Drug Administration’s Adverse Event Reporting System (FAERS). Methods: Disproportionality analysis and Bayesian analysis were utilized for data mining of the suspected cardiac AEs of TKIs, based on FAERS data from January 2004 to December 2021. Results: A total of 4708 cardiac AEs reports of sorafenib, regorafenib, lenvatinib and cabozantinib were identifed. Among them, 17 cardiac AEs signals were detected in regorafenib, 15 cardiac AEs signals were detected in lenvatinib, 57 cardiac AEs signals were detected in sorafenib while 27 cardiac AEs signals were detected in cabozantinib. Hypertension accounts for the most reported cardiac AE. Lenvatinib appears to induce cardiac failure with the highest signals strength [ROR=7.7(3.46,17.17)]. Acute myocardial infarction were detected in lenvatinib [ROR=7.91(5.64,11.09)] and sorafenib[ROR=2.22(1.74, 2.84)]. Acute coronary syndrome were detected in lenvatinib[ROR=11.57(6.84, 19.58)] and sorafenib [ROR=2.81(1.87,4.24)]. Atrial fibrillation were detected in sorafenib [ROR=1.82(1.55,2.14)] and regorafenib [ROR=1.36(1.03,1.81)]. Meanwhile, aortic dissection were detected in sorafenib [ROR=5.08(3.31,7.8)] and regorafenib [ROR=3.39(1.52,7.56)]. Most patients developed hypertension and cardiac failure within 30 days after TKIs treatment. Patients taking lenvatinib developed acute coronary syndrome increased in the periods of 180 days(64.29%) . Conclusion: Analysis of FAERS provides more precise profile on the characteristics of cardiac AEs after different TKI regimens. Distinct monitoring and appropriate management are needed in the care of the TKIs recipients.

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Section: Discussionmentioning

confidence: 99%

Cardiovascular toxicities following the use of tyrosine kinase inhibitors in Hepatocellular Cancer Patients: A Retrospective, Pharmacovigilance Study

Lai

Wan

Jiao

et al. 2023

Preprint

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“…Immunotherapies and targeted therapies—implying inhibition of human epidermal growth factor receptor 2 (HER2) signaling with either antibodies (trastuzumab, pertuzumab) or TKIs (lapatinib)—have ameliorated survival of patients with HER2-positive breast cancer [ 2 , 13 ]. In addition, 3% to 7% of patients who receive trastuzumab monotherapy develop cardiac dysfunction (from asymptomatic LVEF decline to HF), which is usually reversible with drug interruption and/or HF treatment [ 2 ].…”

Section: The Spectrum Of Cardiotoxicitymentioning

confidence: 99%

Exploring the Cardiotoxicity Spectrum of Anti-Cancer Treatments: Definition, Classification, and Diagnostic Pathways

Mauro

Capone

Cocchia

et al. 2023

JCM

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Early detection and treatment of cancer have led to a noticeable reduction in both mortality and morbidity. However, chemotherapy and radiotherapy could exert cardiovascular (CV) side effects, impacting survival and quality of life, independent of the oncologic prognosis. In this regard, a high clinical index of suspicion is required by the multidisciplinary care team in order to trigger specific laboratory tests (namely natriuretic peptides and high-sensitivity cardiac troponin) and appropriate imaging techniques (transthoracic echocardiography along with cardiac magnetic resonance, cardiac computed tomography, and nuclear testing (if clinically indicated)), leading to timely diagnosis. In the near future, we do expect a more tailored approach to patient care within the respective community along with the widespread implementation of digital health tools.

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“…Immunotherapies and targeted therapies implying the inhibition of human epidermal growth factor receptor 2 (HER2) signaling with either antibodies (e.g., trastuzumab and pertuzumab) or small molecule tyrosine kinase inhibitors (TKIs as lapatinib) have improved the outcomes of patients with HER2-positive (+) breast cancer [ 13 , 14 ]. Trastuzumab is a monoclonal antibody binding to the HER2 extracellular domain [ 15 ]; HER2 is part of the transmembrane epidermal growth factor receptor tyrosine kinases (ErbB) with a role in growth, proliferation, and repair [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Cardiovascular Side Effects of Anthracyclines and HER2 Inhibitors among Patients with Breast Cancer: A Multidisciplinary Stepwise Approach for Prevention, Early Detection, and Treatment

Mauro

Capone

Cocchia

et al. 2023

JCM

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Cardiovascular (CV) diseases (CVD) are a major cause of long-term morbidity and mortality affecting life expectancy amongst cancer survivors. In recent years, because of the possibility of early diagnosis and the increased efficacy of neo-adjuvant and adjuvant systemic treatments (targeting specific molecular pathways), the high percentage of survival from breast cancer led CVD to become the first cause of death among survivors. Therefore, it is mandatory to adopt cardioprotective strategies to minimize CV side effects and CVD in general in breast cancer patients. Cancer therapeutics-related cardiac dysfunction (CTRCD) is a common group of side effects of chemotherapeutics widely employed in breast cancer (e.g., anthracycline and human epidermal growth factor receptor 2 inhibitors). The aim of the present manuscript is to propose a pragmatic multidisciplinary stepwise approach for prevention, early detection, and treatment of cardiotoxicity in patients with breast cancer.

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Intracellular Signaling Pathways Mediating Tyrosine Kinase Inhibitor Cardiotoxicity

Cited by 9 publications

References 118 publications

Cardiovascular toxicities following the use of tyrosine kinase inhibitors in Hepatocellular Cancer Patients: A Retrospective, Pharmacovigilance Study

Cardiovascular toxicities following the use of tyrosine kinase inhibitors in Hepatocellular Cancer Patients: A Retrospective, Pharmacovigilance Study

Exploring the Cardiotoxicity Spectrum of Anti-Cancer Treatments: Definition, Classification, and Diagnostic Pathways

Cardiovascular Side Effects of Anthracyclines and HER2 Inhibitors among Patients with Breast Cancer: A Multidisciplinary Stepwise Approach for Prevention, Early Detection, and Treatment

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