HER2-Targeted Therapy—From Pathophysiology to Clinical Manifestation: A Narrative Review
Trastuzumab is the primary treatment for all stages of HER2-overexpressing breast cancer in patients. Though discovered over 20 years ago, trastuzumab-induced cardiotoxicity (TIC) remains a research topic in cardio-oncology. This review explores the pathophysiological basis of TIC and its clinical m...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Journal of Cardiovascular Development and Disease |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2308-3425/10/12/489 |
| _version_ | 1797380537010094080 |
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| author | Svetoslava Elefterova Slavcheva Atanas Angelov |
| author_facet | Svetoslava Elefterova Slavcheva Atanas Angelov |
| author_sort | Svetoslava Elefterova Slavcheva |
| collection | DOAJ |
| description | Trastuzumab is the primary treatment for all stages of HER2-overexpressing breast cancer in patients. Though discovered over 20 years ago, trastuzumab-induced cardiotoxicity (TIC) remains a research topic in cardio-oncology. This review explores the pathophysiological basis of TIC and its clinical manifestations. Their understanding is paramount for early detection and cardioprotective treatment. Trastuzumab renders cardiomyocytes susceptible by inhibiting the cardioprotective NRG-1/HER2/HER4 signaling pathway. The drug acts on HER2-receptor-expressing cardiomyocytes, endothelium, and cardiac progenitor cells (see the Graphical Abstract). The activation of immune cells, fibroblasts, inflammation, and neurohormonal systems all contribute to the evolution of TIC. A substantial amount of research demonstrates that trastuzumab induces overt and subclinical left ventricular (LV) systolic failure. Data suggest the development of right ventricular damage, LV diastolic dysfunction, and heart failure with preserved ejection fraction. Further research is needed to define a chronological sequence of cardiac impairments to guide the proper timing of cardioprotection implementation. |
| first_indexed | 2024-03-08T20:39:41Z |
| format | Article |
| id | doaj.art-434777148dd1413aa180120c7ad53747 |
| institution | Directory Open Access Journal |
| issn | 2308-3425 |
| language | English |
| last_indexed | 2024-03-08T20:39:41Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Cardiovascular Development and Disease |
| spelling | doaj.art-434777148dd1413aa180120c7ad537472023-12-22T14:16:43ZengMDPI AGJournal of Cardiovascular Development and Disease2308-34252023-12-01101248910.3390/jcdd10120489HER2-Targeted Therapy—From Pathophysiology to Clinical Manifestation: A Narrative ReviewSvetoslava Elefterova Slavcheva0Atanas Angelov1First Department of Internal Diseases, EC Cardiology, Faculty of Medicine, Medical University “Prof. Dr. Paraskev Stoyanov”, 9000 Varna, BulgariaFirst Department of Internal Diseases, EC Cardiology, Faculty of Medicine, Medical University “Prof. Dr. Paraskev Stoyanov”, 9000 Varna, BulgariaTrastuzumab is the primary treatment for all stages of HER2-overexpressing breast cancer in patients. Though discovered over 20 years ago, trastuzumab-induced cardiotoxicity (TIC) remains a research topic in cardio-oncology. This review explores the pathophysiological basis of TIC and its clinical manifestations. Their understanding is paramount for early detection and cardioprotective treatment. Trastuzumab renders cardiomyocytes susceptible by inhibiting the cardioprotective NRG-1/HER2/HER4 signaling pathway. The drug acts on HER2-receptor-expressing cardiomyocytes, endothelium, and cardiac progenitor cells (see the Graphical Abstract). The activation of immune cells, fibroblasts, inflammation, and neurohormonal systems all contribute to the evolution of TIC. A substantial amount of research demonstrates that trastuzumab induces overt and subclinical left ventricular (LV) systolic failure. Data suggest the development of right ventricular damage, LV diastolic dysfunction, and heart failure with preserved ejection fraction. Further research is needed to define a chronological sequence of cardiac impairments to guide the proper timing of cardioprotection implementation.https://www.mdpi.com/2308-3425/10/12/489cardiotoxicitytrastuzumabpathophysiologyclinical manifestation |
| spellingShingle | Svetoslava Elefterova Slavcheva Atanas Angelov HER2-Targeted Therapy—From Pathophysiology to Clinical Manifestation: A Narrative Review Journal of Cardiovascular Development and Disease cardiotoxicity trastuzumab pathophysiology clinical manifestation |
| title | HER2-Targeted Therapy—From Pathophysiology to Clinical Manifestation: A Narrative Review |
| title_full | HER2-Targeted Therapy—From Pathophysiology to Clinical Manifestation: A Narrative Review |
| title_fullStr | HER2-Targeted Therapy—From Pathophysiology to Clinical Manifestation: A Narrative Review |
| title_full_unstemmed | HER2-Targeted Therapy—From Pathophysiology to Clinical Manifestation: A Narrative Review |
| title_short | HER2-Targeted Therapy—From Pathophysiology to Clinical Manifestation: A Narrative Review |
| title_sort | her2 targeted therapy from pathophysiology to clinical manifestation a narrative review |
| topic | cardiotoxicity trastuzumab pathophysiology clinical manifestation |
| url | https://www.mdpi.com/2308-3425/10/12/489 |
| work_keys_str_mv | AT svetoslavaelefterovaslavcheva her2targetedtherapyfrompathophysiologytoclinicalmanifestationanarrativereview AT atanasangelov her2targetedtherapyfrompathophysiologytoclinicalmanifestationanarrativereview |