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Doxorubicin: The Good, the Bad and the Ugly Effect
Abstract
The anthracycline doxorubicin (DOX) is widely used in chemotherapy due to its efficacy in fighting a wide range of cancers such as carcinomas, sarcomas and hematological cancers. Despite extensive clinical utilization, the mechanisms of action of DOX remain under intense debate. A growing body of evidence supports the view that this drug can be a double-edge sword. Indeed, injury to nontargeted tissues often complicates cancer treatment by limiting therapeutic dosages of DOX and diminishing the quality of patients' life during and after DOX treatment. The literature shows that the heart is a preferential target of DOX toxicity. However, this anticancer drug also affects other organs like the brain, kidney and liver. This review is mainly devoted to discuss the mechanisms underlying not only DOX beneficial effects but also its toxic outcomes. Additionally, clinical studies focusing the therapeutic efficacy and side effects of DOX treatment will be discussed. Finally, some potential strategies to attenuate DOX-induced toxicity will be debated.
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“The latter produces multiple severe side effects including the cumulative cardiotoxicity, acute nausea and vomiting, gastrointestinal disturbances, alopecia baldness, and neurologic disturbances (Carvalho et al., 2009).”
From An Arthropod Hormone, Ecdysterone, Inhibits the Growth of Breast Cancer Cells via Different Mechanisms (2020) · cites this paper as Carvalho et al., 2009
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Hanušová, V., Králová, V., Schröterová, L., et al. (2010) · Xenobiotica · doi:10.3109/00498254.2010.508821 · Cited by 16
“Cancer cell mortality has been correlated with both dose and exposure time, but DOX systemic toxicity, especially cardiotoxicity, strongly limits the maximal therapeutic dose of DOX (Carvalho et al., 2009).”
BackgroundZayed, G., Kamal, I., Abdelhafez, W. A., et al. (2018) · Pharmaceutical Research · doi:10.1007/s11095-018-2393-6 · Cited by 16
Smith, M. R., Chacko, B. K., Johnson, M. S., et al. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101311 · Cited by 16
Zhao, Y.-Q., Zhang, L., Zhao, G., Chen, Y., Sun, K., & Wang, B. (2019) · Journal of Functional Foods · doi:10.1016/j.jff.2019.103542 · Cited by 16
Isoliquiritigenin as a modulator of the Nrf2 signaling pathway: potential therapeutic implications
Qiu, M., Ma, K., Zhang, J., Zhao, Z., Wang, S., Wang, Q., & Xu, H. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1395735 · Cited by 18
“Given that the liver serves as a crucial metabolic organ in the human body, it has been observed that during doxorubicin therapy, the liver is exposed to high concentrations of the drug and experiences the most pronounced impact (Carvalho et al., 2009).”
Background
Metadata
- Authors
- Carvalho, C., Santos, R., Cardoso, S., Correia, S., Oliveira, P., Santos, M., & Moreira, P.
- Affiliations
- Centro de Neurociências e Biologia Celular (PT)
- Corresponding author
- Moreira, Paula
- Venue
- Current Medicinal Chemistry
- Publisher
- Bentham Science Publishers Ltd.
- Published
- 2009-09-01
- Volume
- 16
- Issue
- 25
- Pages
- 3267-3285
- ISSN
- 0929-8673 (ISSN-L)
- OpenAlex
- W2102897174
- Cited by
- 1,509
- References
- 0
- Citations by year
- 2026: 102 · 2025: 147 · 2024: 174 · 2023: 169 · 2022: 153 · 2021: 150 · 2020: 120 · 2019: 85 · 2018: 84 · 2017: 53 · 2016: 63 · 2015: 62 · 2014: 43 · 2013: 35 · 2012: 29
- FWCI
- 14.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Medicinal Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Chemotherapy-induced cardiotoxicity and mitigation
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Bioactive Compounds and Antitumor Agents
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer therapeutics and mechanisms
- Keywords
- doxorubicin, anthracyclines, cardiotoxicity, drug toxicity mechanisms, anticancer mechanism, neurotoxicity, nephrotoxicity, hepatotoxicity, chemotherapy side effects
- MeSH terms
- Antibiotics, Antineoplastic, Doxorubicin, Humans, Molecular Conformation, Neoplasms
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