Anthracycline‑induced cardiotoxicity in the chemotherapy treatment of breast cancer: Preventive strategies and treatment (Review)

Cai, Fengfeng; Luis, Manuel Antonio Falar; Lin, Xinhua; Wang, Minghong; Cai, Lei; Cen, Chunmei; Biskup, Ewelina

doi:10.3892/mco.2019.1854

Cited by 110 publications

(99 citation statements)

References 53 publications

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Section: Introductionmentioning

confidence: 99%

“…DOX is a highly potent anticancer drug; however, its serious side-effects, and especially its cardiotoxicity, restricts its use in many situations [12]. The latter problem has been resolved by the construction of PEGylated DOX-loaded liposomes, which realize altered DOX pharmacokinetics and consequently, reduced toxicity [12][13][14]. The easy loading of high amounts of DOX in pre-formed empty PEG-liposomes by an active-loading protocol [15,16] has highly contributed to the development of the long-circulating liposomal formulation of DOX, which is in clinical use for more than 25 years.…”

Section: Introductionmentioning

confidence: 99%

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Preparation, Physicochemical Properties, and In Vitro Toxicity towards Cancer Cells of Novel Types of Arsonoliposomes

et al. 2020

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Arsonoliposomes (ARSL) are liposomes that incorporate arsonolipids (ARS) in their membranes. They have demonstrated significant toxicity towards cancer cells, while being less toxic towards normal cells. In this study, we sought to investigate the possibility to prepare novel types of arsonoliposomes (ARSL) by incorporating a lipidic derivative of curcumin (TREG) in their membrane, and/or by loading the vesicles with doxorubicin (DOX). The final aim of our studies is to develop novel types of ARSL with improved pharmacokinetics/targeting potential and anticancer activity. TREG was incorporated in ARSL and their integrity during incubation in buffer and serum proteins was studied by monitoring calcein latency. After evaluation of TREG-ARSL stability, the potential to load DOX into ARSL and TREG-ARSL, using the active loading protocol, was studied. Loading was performed at two temperatures (40 °C and 60 °C) and different time periods of co-incubation (of empty vesicles with DOX). Calculation of DOX entrapment efficiency (%) was based on initial and final drug/lipid ratios. The cytotoxic activity of DOX-ARSL was tested towards B16F10 cells (mouse melanoma cells), LLC (Lewis Lung carcinoma cells), and HEK-293 (Human embryonic kidney cells). Results show that TREG-ARSL have slightly larger size but similar surface charge with ARSL and that they are both highly stable during storage at 4 °C for 56 d. Interestingly, the inclusion of TREG in ARSL conferred increased stability to the vesicles towards disruptive effects of serum proteins. The active-loading protocol succeeded to encapsulate high amounts of DOX into ARSL as well as TREG-LIP and TREG-ARSL, while the release profile of DOX from the novel liposome types was similar to that demonstrated by DOX-LIP. The cytotoxicity study results are particularly encouraging, since DOX-ARSL were less toxic towards the (normal) HEK cells compared to the two cancer cell-types. Furthermore, DOX-ARSL demonstrated lower toxicities (at all concentrations tested) for HEK cells, compared to that of the corresponding mixtures of free DOX and empty ARSL, while the opposite was true for the cancer cells (in most cases). The current results justify further in vivo exploitation of DOX-ARSL, as well as TREGARSL as anticancer therapeutic systems.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Preparation, Physicochemical Properties, and In Vitro Toxicity towards Cancer Cells of Novel Types of Arsonoliposomes

et al. 2020

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“…AIC can manifest acutely, early after infusion, strongly compromising cancer treatment since it may require dose modification or even cessation of anticancer therapies (12). Almost 30% of patients are affected by this type of cardiotoxicity, that is characterized by electrocardiogram abnormalities, including atypical ST changes, reduced QRS voltage, tachycardia, and supraventricular premature beats.…”

Section: Aic: From Definition To Current Treatmentmentioning

confidence: 99%

“…Dexrazoxane is not only one of the most studied cardioprotective adjuvant for DOX chemotherapy, but it is also the only Food and Drug Administration (FDA)-and European Medicines Agency (EMA)-approved drug for AIC prevention (12,52). Thanks to its ability to act as an iron-chelator, dexrazoxane inhibits the production of ROS ensuing from the interaction between ANTs and non-heme iron, ultimately alleviating DOX-induced mitochondrial oxidative stress [ Figure 1; (53, 54)].…”

Section: Dexrazoxanementioning

confidence: 99%

“…It was also reported that dexrazoxane alone does not increase the risk of second primary malignancies (SPMs), which are instead related to the usage of three Top2 inhibitors used in combination (doxorubicin, etoposide, and dexrazoxane) and mostly etoposide (71). For these reasons, EMA has approved the administration of dexrazoxane to children supposed to be given more than 300 mg/m 2 of ANTs (12,52,68).…”

Section: Dexrazoxanementioning

confidence: 99%

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Mechanisms of Anthracycline-Induced Cardiotoxicity: Is Mitochondrial Dysfunction the Answer?

Murabito

Hirsch

Ghigo

2020

Front. Cardiovasc. Med.

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Cardiac side effects are a major drawback of anticancer therapies, often requiring the use of low and less effective doses or even discontinuation of the drug. Among all the drugs known to cause severe cardiotoxicity are anthracyclines that, though being the oldest chemotherapeutic drugs, are still a mainstay in the treatment of solid and hematological tumors. The recent expansion of the field of Cardio-Oncology, a branch of cardiology dealing with prevention or treatment of heart complications due to cancer treatment, has greatly improved our knowledge of the molecular mechanisms behind anthracycline-induced cardiotoxicity (AIC). Despite excessive generation of reactive oxygen species was originally believed to be the main cause of AIC, recent evidence points to the involvement of a plethora of different mechanisms that, interestingly, mainly converge on deregulation of mitochondrial function. In this review, we will describe how anthracyclines affect cardiac mitochondria and how these organelles contribute to AIC. Furthermore, we will discuss how drugs specifically targeting mitochondrial dysfunction and/or mitochondria-targeted drugs could be therapeutically exploited to treat AIC.

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Identification of Risk of Cardiovascular Disease by Automatic Quantification of Coronary Artery Calcifications on Radiotherapy Planning CT Scans in Patients With Breast Cancer

et al. 2021

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IMPORTANCE Cardiovascular disease (CVD) is common in patients treated for breast cancer, especially in patients treated with systemic treatment and radiotherapy and in those with preexisting CVD risk factors. Coronary artery calcium (CAC), a strong independent CVD risk factor, can be automatically quantified on radiotherapy planning computed tomography (CT) scans and may help identify patients at increased CVD risk.OBJECTIVE To evaluate the association of CAC with CVD and coronary artery disease (CAD) in patients with breast cancer. DESIGN, SETTING, AND PARTICIPANTSIn this multicenter cohort study of 15 915 patients with breast cancer receiving radiotherapy between 2005 and 2016 who were followed until December 31, 2018, age, calendar year, and treatment-adjusted Cox proportional hazard models were used to evaluate the association of CAC with CVD and CAD.EXPOSURES Overall CAC scores were automatically extracted from planning CT scans using a deep learning algorithm. Patients were classified into Agatston risk categories (0, 1-10, 11-100, 101-399, >400 units). MAIN OUTCOMES AND MEASURESOccurrence of fatal and nonfatal CVD and CAD were obtained from national registries. RESULTSOf the 15 915 participants included in this study, the mean (SD) age at CT scan was 59.0 (11.2; range, 22-95) years, and 15 879 (99.8%) were women. Seventy percent (n = 11 179) had no CAC. Coronary artery calcium scores of 1 to 10, 11 to 100, 101 to 400, and greater than 400 were present in 10.0% (n = 1584), 11.5% (n = 1825), 5.2% (n = 830), and 3.1% (n = 497) respectively. After a median follow-up of 51.2 months, CVD risks increased from 5.2% in patients with no CAC to 28.2% in patients with CAC scores higher than 400. After adjustment, CVD risk increased with higher CAC score (hazard ratio [HR] CAC = 1-10 = 1.1; 95% CI, 0.9-1.4; HR CAC = 11-100 = 1.8; 95% CI, 1.5-2.1; HR CAC = 101-400 = 2.1; 95% CI, 1.7-2.6; and HR CAC>400 = 3.4; 95% CI, 2.8-4.2). Coronary artery calcium was particularly strongly associated with CAD (HR CAC>400 = 7.8; 95% CI, 5.5-11.2). The association between CAC and CVD was strongest in patients treated with anthracyclines (HR CAC>400 = 5.8; 95% CI, 3.0-11.4) and patients who received a radiation boost (HR CAC>400 = 6.1; 95% CI, 3.8-9.7).CONCLUSIONS AND RELEVANCE This cohort study found that coronary artery calcium on breast cancer radiotherapy planning CT scan results was associated with CVD, especially CAD. Automated CAC scoring on radiotherapy planning CT scans may be used as a fast and low-cost tool to identify patients with breast cancer at increased risk of CVD, allowing implementing CVD risk-mitigating strategies with the aim to reduce the risk of CVD burden after breast cancer.

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Anthracycline‑induced cardiotoxicity in the chemotherapy treatment of breast cancer: Preventive strategies and treatment (Review)

Cited by 110 publications

References 53 publications

Preparation, Physicochemical Properties, and In Vitro Toxicity towards Cancer Cells of Novel Types of Arsonoliposomes

Preparation, Physicochemical Properties, and In Vitro Toxicity towards Cancer Cells of Novel Types of Arsonoliposomes

Mechanisms of Anthracycline-Induced Cardiotoxicity: Is Mitochondrial Dysfunction the Answer?

Identification of Risk of Cardiovascular Disease by Automatic Quantification of Coronary Artery Calcifications on Radiotherapy Planning CT Scans in Patients With Breast Cancer

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