An update of the molecular mechanisms underlying doxorubicin plus trastuzumab induced cardiotoxicity
| Autor: | Vera Marisa Costa, Miguel Anjos, Mário Santos, Marta Fontes-Oliveira, Rita Ferreira |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Receptor ErbB-2 Neuregulin-1 Antineoplastic Agents 030226 pharmacology & pharmacy General Biochemistry Genetics and Molecular Biology 03 medical and health sciences 0302 clinical medicine Trastuzumab Neoplasms Antineoplastic Combined Chemotherapy Protocols medicine Animals Humans Doxorubicin Myocytes Cardiac General Pharmacology Toxicology and Pharmaceutics Protein kinase A Protein kinase B PI3K/AKT/mTOR pathway Cardiotoxicity business.industry General Medicine Oxidative Stress 030104 developmental biology Cancer research Signal transduction business medicine.drug Signal Transduction |
| Zdroj: | Life sciences. 280 |
| ISSN: | 1879-0631 |
| Popis: | Cardiotoxicity is a major side effect of the chemotherapeutic drug doxorubicin (Dox), which is further exacerbated when it is combined with trastuzumab, a standard care approach for Human Epidermal growth factor Receptor-type 2 (HER2) positive cancer patients. However, the molecular mechanisms of the underlying cardiotoxicity of this combination are still mostly elusive. Increased oxidative stress, impaired energetic substrate uses and topoisomerase IIB inhibition are among the biological processes proposed to explain Dox-induced cardiomyocyte dysfunction. Since cardiomyocytes express HER2, trastuzumab can also damage these cells by interfering with neuroregulin-1 signaling and mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt and focal adhesion kinase (FAK)-dependent pathways. Nevertheless, Dox and trastuzumab target other cardiac cell types, such as endothelial cells, fibroblasts, cardiac progenitor cells and leukocytes, which can contribute to the clinical cardiotoxicity observed. This review aims to summarize the current knowledge on the cardiac signaling pathways modulated by these two antineoplastic drugs highly used in the management of breast cancer, not only focusing on cardiomyocytes but also to broaden the knowledge of the potential impact on other cells found in the heart. |
| Databáze: | OpenAIRE |
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