Publication: EFFECTS OF EPIDERMAL GROWTH FACTOR RECEPTOR INHIBITION ON DOXORUBICIN-INDUCED CARDIOTOXICITY
| dc.contributor.author | LEE SHU NING | |
| dc.date.accessioned | 2024-03-09T00:22:33Z | |
| dc.date.available | 2024-03-09T00:22:33Z | |
| dc.date.issued | 2023 | |
| dc.description.abstract | Potential cardiotoxicity remained the crucial factor limiting the clinical use of doxorubicin-based chemotherapy, despite their effectiveness in various malignancies. Combination therapy involving doxorubicin has therefore emerged as a potential therapeutic option, in an effort to enhance anticancer efficiency at the same time minimise cardiovascular side effects. Epidermal growth factor receptor (EGFR) inhibitors are a group of tyrosine kinase small molecules inhibitor recently approved for clinical use in cancer therapy. The combination of doxorubicin and EGFR inhibitors has shown great promise by demonstrating enhanced anticancer effects and ability to reverse chemoresistance associated with doxorubicin. Although EGFR inhibitor alone displayed minimal cardiotoxicity, it has raised concern that concurrent use would potentiate doxorubicin-induced cardiotoxicity. This study therefore aimed to investigate possible synergistic cardiotoxic effect of doxorubicin and EGFR inhibition. By utilising human AC16 cardiomyocytes, we first assessed the EGFR inhibitors including erlotinib, gefitinib, afatinib and lapatinib, with concentration ranging from 1-100 μM for erlotinib, gefitinib and lapatinib whereas 1-10 μM for afatinib, which revealed that all EGFR inhibitors tested elicited cytotoxic responses towards cardiomyocytes at different potency levels. When combined with doxorubicin, only erlotinib was found to synergise doxorubicin-induced cardiotoxicity. Further cell apoptotic assay confirmed this synergism, suggesting that erlotinib may enhance apoptosis induced by doxorubicin. Intriguingly, this synergism was not observed in gefitinib, afatinib and lapatinib, which proposed that synergistic cardiotoxicity may be specific to each inhibitor instead of a drug-class effect. In summary, this study suggested that the clinical use of concurrent erlotinib and doxorubicin should be approached with caution due to the possibility of increased cardiotoxicity, and this warrants further mechanistic studies for understanding the precise underlying mechanisms and developing cardioprotective agents. | |
| dc.identifier.uri | https://hdl.handle.net/20.500.14377/36072 | |
| dc.language.iso | en | |
| dc.publisher | International Medical University | |
| dc.subject | Cardiotoxicity | |
| dc.subject | Drug Therapy | |
| dc.subject | ErbB Receptors | |
| dc.subject | Doxorubicin | |
| dc.subject | Erlotinib Hydrochloride | |
| dc.title | EFFECTS OF EPIDERMAL GROWTH FACTOR RECEPTOR INHIBITION ON DOXORUBICIN-INDUCED CARDIOTOXICITY | |
| dc.type | Thesis | |
| dspace.entity.type | Publication | |
| oairecerif.author.affiliation | #PLACEHOLDER_PARENT_METADATA_VALUE# |