Erlotinib-Induced Cardiomyopathy in a Patient with Metastatic Non-Small Cell Lung Cancer

Nagashio, Kenji; Tajiri, Kazuko; Sato, Kimi; Ieda, Masaki

doi:10.1536/ihj.21-130

Cited by 9 publications

(4 citation statements)

References 10 publications

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“…Based on our results, we anticipate that short-term EGFR inhibition can be beneficial in the setting of AC. Furthermore, unlike other EGFR inhibitors, reports of adverse cardiac effects after erlotinib treatment are very rare (Kenigsberg et al, 2017, Stuhlmiller et al, 2017, Barish et al, 2019, Nagashio et al, 2021). Taken together, we conclude that inhibiting EGFR, thereby enhancing desmosome assembly via ROCK stabilizes desmosome integrity and cardiomyocyte cohesion.…”

Section: Discussionmentioning

confidence: 99%

EGFR inhibition led ROCK activation enhances desmosome assembly and cohesion in cardiomyocytes

Shoykhet

Dervishi

Menauer

et al. 2022

Preprint

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The epidermal growth factor receptor (EGFR) is a ubiquitously expressed receptor tyrosine kinase, which is dysregulated in several kinds of cancer and heart diseases. Arrhythmogenic cardiomyopathy (AC) is a familial heart disease in part caused by impaired desmosome turnover. Thus, stabilization of desmosome integrity, may provide potential new treatment options. Desmosomes, apart from cellular cohesion, provide the structural framework of a signaling hub. Here, we investigated the role of EGFR inhibition on cardiomyocyte cohesion under physiological and pathophysiological conditions using the murine plakoglobin knockout AC model, in which EGFR was upregulated. EGFR inhibition led to enhanced cardiomyocyte cohesion. Immunoprecipitation showed an interaction of EGFR and desmoglein 2 (DSG2). Immunostaining and AFM revealed enhanced DSG2 localization and binding at cell borders upon EGFR inhibition. Enhanced area composita length and desmosome assembly was observed upon EGFR inhibition, confirmed by enhanced DSG2 and desmoplakin (DP) recruitment to the cell borders. Thus, inhibiting EGFR, thereby stabilizing desmosome integrity, may provide new treatment options for AC.

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Section: Discussionmentioning

confidence: 99%

EGFR inhibition led ROCK activation enhances desmosome assembly and cohesion in cardiomyocytes

Shoykhet

Dervishi

Menauer

et al. 2022

Preprint

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show abstract

“…Based on our results, we anticipate that EGFR inhibition can be beneficial in the setting of AC. Furthermore, unlike other EGFR inhibitors, reports of adverse cardiac effects after erlotinib treatment are very rare ( 16 , 73 – 75 ). Taken together, we conclude that inhibiting EGFR, thereby enhancing desmosome assembly via ROCK, stabilizes desmosome integrity and cardiomyocyte cohesion.…”

Section: Discussionmentioning

confidence: 99%

EGFR inhibition leads to enhanced desmosome assembly and cardiomyocyte cohesion via ROCK activation

Shoykhet¹,

Dervishi²,

Menauer³

et al. 2023

JCI Insight

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Arrhythmogenic cardiomyopathy (AC) is a familial heart disease partly caused by impaired desmosome turnover. Thus, stabilization of desmosome integrity may provide potential new treatment options. Desmosomes, apart from cellular cohesion, provide the structural framework of a signaling hub. Here, we investigated the role of the epidermal growth factor receptor (EGFR) in cardiomyocyte cohesion. We inhibited EGFR under physiological and pathophysiological conditions using the murine plakoglobin knockout AC model, in which EGFR was upregulated. EGFR inhibition enhanced cardiomyocyte cohesion.Immunoprecipitation showed an interaction of EGFR and desmoglein 2 (DSG2).Immunostaining and AFM revealed enhanced DSG2 localization and binding at cell borders upon EGFR inhibition. Enhanced area composita length and desmosome assembly were observed upon EGFR inhibition, confirmed by enhanced DSG2 and desmoplakin (DP) recruitment to cell borders. PamGene Kinase assay performed in HL-1 cells treated with Erlotinib, an EGFR inhibitor, revealed upregulation of RhoA associated protein kinase (ROCK). Erlotinib-mediated desmosome assembly and cardiomyocyte cohesion were abolished upon ROCK inhibition. Thus, inhibiting EGFR, thereby stabilizing desmosome integrity via ROCK, might provide new treatment options for AC.

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“…Pinquie et al ( 18) also reported a new case of dilated cardiomyopathy associated with erlotinib therapy, suggesting that long-term maintenance therapy with erlotinib may cause dilated cardiomyopathy. Kenji et al (19) report a case of cardiomyopathy that developed during erlotinib treatment for NSCLC. Two months after erlotinib initiation, our 70year-old female patient complained of progressive dyspnea, and a diagnostic endomyocardial biopsy confirmed non-specific cardiomyopathy, indicating erlotinib-induced cardiomyopathy.…”

Section: Erlotinibmentioning

confidence: 99%

“…Kenji et al. ( 19 ) report a case of cardiomyopathy that developed during erlotinib treatment for NSCLC. Two months after erlotinib initiation, our 70-year-old female patient complained of progressive dyspnea, and a diagnostic endomyocardial biopsy confirmed non-specific cardiomyopathy, indicating erlotinib-induced cardiomyopathy.…”

Section: Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitorsmentioning

confidence: 99%

EGFR-TKIs - induced cardiotoxicity in NSCLC: incidence, evaluation, and monitoring

Wang,

Qiu,

Deng

et al. 2024

Front. Oncol.

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The advent of targeted drug therapy has greatly changed the treatment landscape of advanced non-small cell lung cancer(NSCLC), but the cardioxic side effects of targeted drug anti-cancer therapy seriously affect the prognosis of NSCLC, and it has become the second leading cause of death in cancer patients. Therefore, early identification of the cardiotoxic side effects of targeted drugs is crucial for the prevention and treatment of cardiovascular diseases. The cardiotoxic side effects that may be caused by novel targeted drugs epidermal growth factor receptor inhibitors, including thromboembolic events, heart failure, cardiomyopathy, arrhythmia and hypertension, are discussed, and the mechanisms of their respective adverse cardiovascular reactions are summarized, to provide useful recommendations for cardiac management of patients with advanced lung cancer to maximize treatment outcomes for lung cancer survivors. Clinicians need to balance the risk-benefit ratio between targeted therapy for malignant tumors and drug-induced cardiotoxicity, and evaluate and monitor TKIs-induced cardiotoxicity through electrocardiogram, cardiac imaging, biomarkers, etc., so as to remove the susceptibility risk factors as soon as possible and provide a reference for the clinical use of such drugs in the treatment of malignant tumors.

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Erlotinib-Induced Cardiomyopathy in a Patient with Metastatic Non-Small Cell Lung Cancer

Cited by 9 publications

References 10 publications

EGFR inhibition led ROCK activation enhances desmosome assembly and cohesion in cardiomyocytes

EGFR inhibition led ROCK activation enhances desmosome assembly and cohesion in cardiomyocytes

EGFR inhibition leads to enhanced desmosome assembly and cardiomyocyte cohesion via ROCK activation

EGFR-TKIs - induced cardiotoxicity in NSCLC: incidence, evaluation, and monitoring

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