Anthracyclines/trastuzumab: new aspects of cardiotoxicity and molecular mechanisms
•Anthracyclines and trastuzumab are effective chemotherapies that can cause cardiotoxicity.•Cardiotoxicity is due to a combination of ‘on-target’ and ‘off-target’ effects.•Neuregulin-1 in the microvascular endothelium is involved in cardiotoxicity.•ErbB2 could be a potential target for anticancer th...
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| Vydáno v: | Trends in pharmacological sciences (Regular ed.) Ročník 36; číslo 6; s. 326 - 348 |
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| Hlavní autoři: | , , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
England
Elsevier Ltd
01.06.2015
Elsevier |
| Témata: | |
| ISSN: | 0165-6147, 1873-3735, 1873-3735 |
| On-line přístup: | Získat plný text |
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| Abstract | •Anthracyclines and trastuzumab are effective chemotherapies that can cause cardiotoxicity.•Cardiotoxicity is due to a combination of ‘on-target’ and ‘off-target’ effects.•Neuregulin-1 in the microvascular endothelium is involved in cardiotoxicity.•ErbB2 could be a potential target for anticancer therapy.•Heme oxygenase-1 inhibition may be a strategy to enhance the response to chemotherapy.•Notch-1 is a novel target in trastuzumab-resistant breast cancer.
Anticancer drugs continue to cause significant reductions in left ventricular ejection fraction resulting in congestive heart failure. The best-known cardiotoxic agents are anthracyclines (ANTHs) such as doxorubicin (DOX). For several decades cardiotoxicity was almost exclusively associated with ANTHs, for which cumulative dose-related cardiac damage was the use-limiting step. Human epidermal growth factor (EGF) receptor 2 (HER2; ErbB2) has been identified as an important target for breast cancer. Trastuzumab (TRZ), a humanized anti-HER2 monoclonal antibody, is currently recommended as first-line treatment for patients with metastatic HER2+ tumors. The use of TRZ may be limited by the development of drug intolerance, such as cardiac dysfunction. Cardiotoxicity has been attributed to free-iron-based, radical-induced oxidative stress. Many approaches have been promoted to minimize these serious side effects, but they are still clinically problematic. A new approach to personalized medicine for cancer that involves molecular screening for clinically relevant genomic alterations and genotype-targeted treatments is emerging. |
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| AbstractList | Highlights•Anthracyclines and trastuzumab are effective chemotherapies that can cause cardiotoxicity. •Cardiotoxicity is due to a combination of ‘on-target’ and ‘off-target’ effects. •Neuregulin-1 in the microvascular endothelium is involved in cardiotoxicity. •ErbB2 could be a potential target for anticancer therapy. •Heme oxygenase-1 inhibition may be a strategy to enhance the response to chemotherapy. •Notch-1 is a novel target in trastuzumab-resistant breast cancer. •Anthracyclines and trastuzumab are effective chemotherapies that can cause cardiotoxicity.•Cardiotoxicity is due to a combination of ‘on-target’ and ‘off-target’ effects.•Neuregulin-1 in the microvascular endothelium is involved in cardiotoxicity.•ErbB2 could be a potential target for anticancer therapy.•Heme oxygenase-1 inhibition may be a strategy to enhance the response to chemotherapy.•Notch-1 is a novel target in trastuzumab-resistant breast cancer. Anticancer drugs continue to cause significant reductions in left ventricular ejection fraction resulting in congestive heart failure. The best-known cardiotoxic agents are anthracyclines (ANTHs) such as doxorubicin (DOX). For several decades cardiotoxicity was almost exclusively associated with ANTHs, for which cumulative dose-related cardiac damage was the use-limiting step. Human epidermal growth factor (EGF) receptor 2 (HER2; ErbB2) has been identified as an important target for breast cancer. Trastuzumab (TRZ), a humanized anti-HER2 monoclonal antibody, is currently recommended as first-line treatment for patients with metastatic HER2+ tumors. The use of TRZ may be limited by the development of drug intolerance, such as cardiac dysfunction. Cardiotoxicity has been attributed to free-iron-based, radical-induced oxidative stress. Many approaches have been promoted to minimize these serious side effects, but they are still clinically problematic. A new approach to personalized medicine for cancer that involves molecular screening for clinically relevant genomic alterations and genotype-targeted treatments is emerging. Anticancer drugs continue to cause significant reductions in left ventricular ejection fraction resulting in congestive heart failure. The best-known cardiotoxic agents are anthracyclines (ANTHs) such as doxorubicin (DOX). For several decades cardiotoxicity was almost exclusively associated with ANTHs, for which cumulative dose-related cardiac damage was the use-limiting step. Human epidermal growth factor (EGF) receptor 2 (HER2; ErbB2) has been identified as an important target for breast cancer. Trastuzumab (TRZ), a humanized anti-HER2 monoclonal antibody, is currently recommended as first-line treatment for patients with metastatic HER2(+) tumors. The use of TRZ may be limited by the development of drug intolerance, such as cardiac dysfunction. Cardiotoxicity has been attributed to free-iron-based, radical-induced oxidative stress. Many approaches have been promoted to minimize these serious side effects, but they are still clinically problematic. A new approach to personalized medicine for cancer that involves molecular screening for clinically relevant genomic alterations and genotype-targeted treatments is emerging.Anticancer drugs continue to cause significant reductions in left ventricular ejection fraction resulting in congestive heart failure. The best-known cardiotoxic agents are anthracyclines (ANTHs) such as doxorubicin (DOX). For several decades cardiotoxicity was almost exclusively associated with ANTHs, for which cumulative dose-related cardiac damage was the use-limiting step. Human epidermal growth factor (EGF) receptor 2 (HER2; ErbB2) has been identified as an important target for breast cancer. Trastuzumab (TRZ), a humanized anti-HER2 monoclonal antibody, is currently recommended as first-line treatment for patients with metastatic HER2(+) tumors. The use of TRZ may be limited by the development of drug intolerance, such as cardiac dysfunction. Cardiotoxicity has been attributed to free-iron-based, radical-induced oxidative stress. Many approaches have been promoted to minimize these serious side effects, but they are still clinically problematic. A new approach to personalized medicine for cancer that involves molecular screening for clinically relevant genomic alterations and genotype-targeted treatments is emerging. Anticancer drugs continue to cause significant reductions in left ventricular ejection fraction resulting in congestive heart failure. The best-known cardiotoxic agents are anthracyclines such as doxorubicin. For several decades, cardiotoxicity was almost exclusively associated with anthracyclines, for which cumulative dose-related cardiac damage was the use-limiting step. Human epidermal growth factor receptor 2 (HER2; ErbB2) has been identified as an important target for breast cancer. Trastuzumab (TRZ), a humanized anti-HER2 monoclonal antibody, is currently recommended as first-line treatment for patients with metastatic HER2+ tumours. The use of TRZ may be limited by the development of drug intolerance, such as cardiac dysfunction. Cardiotoxicity has been attributed to free-iron-based, radical-induced oxidative stress. Many approaches have been promoted to minimize these serious side effects, but they are still clinically problematic. A new approach to personalized medicine for cancer that involves molecular screening for clinically relevant genomic alterations and genotype-targeted treatments is emerging. Anticancer drugs continue to cause significant reductions in left ventricular ejection fraction resulting in congestive heart failure. The best-known cardiotoxic agents are anthracyclines (ANTHs) such as doxorubicin (DOX). For several decades cardiotoxicity was almost exclusively associated with ANTHs, for which cumulative dose-related cardiac damage was the use-limiting step. Human epidermal growth factor (EGF) receptor 2 (HER2; ErbB2) has been identified as an important target for breast cancer. Trastuzumab (TRZ), a humanized anti-HER2 monoclonal antibody, is currently recommended as first-line treatment for patients with metastatic HER2(+) tumors. The use of TRZ may be limited by the development of drug intolerance, such as cardiac dysfunction. Cardiotoxicity has been attributed to free-iron-based, radical-induced oxidative stress. Many approaches have been promoted to minimize these serious side effects, but they are still clinically problematic. A new approach to personalized medicine for cancer that involves molecular screening for clinically relevant genomic alterations and genotype-targeted treatments is emerging. |
| Author | Rochette, Luc Vergely, Catherine Gudjoncik, Aurélie Zeller, Marianne Guenancia, Charles Cottin, Yves Hachet, Olivier |
| Author_xml | – sequence: 1 givenname: Luc surname: Rochette fullname: Rochette, Luc email: Luc.rochette@u-bourgogne.fr organization: Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM), Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche 866, Facultés de Médecine et de Pharmacie – Université de Bourgogne, 7 Boulevard Jeanne d’Arc, 21033 Dijon, France – sequence: 2 givenname: Charles surname: Guenancia fullname: Guenancia, Charles organization: Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM), Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche 866, Facultés de Médecine et de Pharmacie – Université de Bourgogne, 7 Boulevard Jeanne d’Arc, 21033 Dijon, France – sequence: 3 givenname: Aurélie surname: Gudjoncik fullname: Gudjoncik, Aurélie organization: Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM), Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche 866, Facultés de Médecine et de Pharmacie – Université de Bourgogne, 7 Boulevard Jeanne d’Arc, 21033 Dijon, France – sequence: 4 givenname: Olivier surname: Hachet fullname: Hachet, Olivier organization: Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM), Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche 866, Facultés de Médecine et de Pharmacie – Université de Bourgogne, 7 Boulevard Jeanne d’Arc, 21033 Dijon, France – sequence: 5 givenname: Marianne surname: Zeller fullname: Zeller, Marianne organization: Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM), Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche 866, Facultés de Médecine et de Pharmacie – Université de Bourgogne, 7 Boulevard Jeanne d’Arc, 21033 Dijon, France – sequence: 6 givenname: Yves surname: Cottin fullname: Cottin, Yves organization: Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM), Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche 866, Facultés de Médecine et de Pharmacie – Université de Bourgogne, 7 Boulevard Jeanne d’Arc, 21033 Dijon, France – sequence: 7 givenname: Catherine surname: Vergely fullname: Vergely, Catherine organization: Laboratoire de Physiopathologie et Pharmacologie Cardio-métaboliques (LPPCM), Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche 866, Facultés de Médecine et de Pharmacie – Université de Bourgogne, 7 Boulevard Jeanne d’Arc, 21033 Dijon, France |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25895646$$D View this record in MEDLINE/PubMed https://ube.hal.science/hal-03434138$$DView record in HAL |
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| Snippet | •Anthracyclines and trastuzumab are effective chemotherapies that can cause cardiotoxicity.•Cardiotoxicity is due to a combination of ‘on-target’ and... Highlights•Anthracyclines and trastuzumab are effective chemotherapies that can cause cardiotoxicity. •Cardiotoxicity is due to a combination of ‘on-target’... Anticancer drugs continue to cause significant reductions in left ventricular ejection fraction resulting in congestive heart failure. The best-known... |
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| SubjectTerms | Advanced Basic Science Animals anthracyclines Anthracyclines - adverse effects Anthracyclines - pharmacology Antineoplastic Agents - adverse effects Antineoplastic Agents - pharmacology Cancer Cardiology and cardiovascular system Cardiotoxicity Drug Synergism Human health and pathology Humans Life Sciences Myocytes, Cardiac - drug effects Myocytes, Cardiac - metabolism Oxidative Stress Pharmaceutical sciences Pharmacology trastuzumab Trastuzumab - adverse effects Trastuzumab - pharmacology |
| Title | Anthracyclines/trastuzumab: new aspects of cardiotoxicity and molecular mechanisms |
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