Search Results (104)

Doxorubicin-induced cardiotoxicity (DIC) significantly constrains the clinical efficacy of anthracycline chemotherapy, primarily through the induction of ferroptosis, an iron-dependent, regulated cell death driven by oxidative stress and lipid peroxidation. However, the upstream regulators of ferroptosis in DIC remain incompletely defined. Cold-inducible RNA-binding protein (CIRBP) exhibits cardioprotective effects in various pathological contexts, but its precise role in ferroptosis-related cardiotoxicity is unknown. This study investigated whether CIRBP mitigates DIC by modulating the ferroptosis pathway via the SLC7A11 (Solute carrier family 7 member 11)/GPX4 (Glutathione peroxidase 4) axis. We observed marked downregulation of CIRBP in cardiac tissues and cardiomyocytes following doxorubicin exposure. CIRBP knockout significantly exacerbated cardiac dysfunction, mitochondrial damage, oxidative stress, and lipid peroxidation, accompanied by increased mortality rates. Conversely, CIRBP overexpression alleviated these pathological changes. Molecular docking and dynamics simulations, supported by transcriptomic analyses, revealed direct binding of CIRBP to the 3′-UTR of Slc7a11 mRNA, enhancing its stability and promoting translation. Correspondingly, CIRBP deficiency markedly suppressed SLC7A11 and GPX4 expression, impairing cystine uptake, glutathione synthesis, and antioxidant defenses, thus amplifying ferroptosis. These ferroptotic alterations were partially reversed by ferroptosis inhibitor ferrostatin-1 (Fer-1). Collectively, this study identifies CIRBP as a critical regulator of ferroptosis in DIC, elucidating a novel post-transcriptional mechanism involving Slc7a11 mRNA stabilization. These findings offer new insights into ferroptosis regulation and highlight CIRBP as a potential therapeutic target for preventing anthracycline-associated cardiac injury. Full article

Background: Many risk factors for cancer therapy-related cardiovascular toxicity overlap with risk factors for atherosclerosis. According to the ESC 2022 Cardio-Oncology Guidelines, coronary computed tomography angiography and coronary artery calcium score are not recommended as part of routine risk assessment prior to oncological treatment. The aim of this study was to prospectively assess the influence of coronary artery calcium score (CAC score) on cancer therapy-related cardiac dysfunction in patients with moderate and high risk of cardiovascular toxicity, qualified for anthracycline treatment. Methods: In all patients, risk factors were collected, laboratory tests, echocardiography with global longitudinal strain (GLS) assessment and coronary artery tomography with coronary artery calcium score were performed. A total of 80 patients were included in the study, of which 77 (96.25%) were followed for an average of 11.5 months. The mean age at baseline was 60.5 years and 72 (93.51%) were women. Results: During observation, five patients (6.49%) died, including two due to heart failure and three due to cancer progression. The majority of patients (59, 76.6%) had breast cancer, 11 (14.3%) were diagnosed with sarcoma and seven (9.1%) with lymphoma. According to the HFA-ICOS risk score, 40 patients (51.9%) were classified as moderate risk (MR), and 37 patients (48.1%) as high risk (HR) for cancer therapy-related cardiovascular toxicity. A CAC score greater than 100 was calculated in 17 (22.1%) patients and greater than 400 in three (3.9%) patients. The CAC score above zero was more common in older patients and in patients classified as high risk (p < 0.001). There was also a significant association between CAC score and hypertension, hyperlipidemia, chronic kidney disease, and the level of NT-proBNP. During 12-month follow-up, mild CTRCD occurred in 38 (49.4%) patients, moderate CTRCD was diagnosed in seven (9.1%), and severe in three (3.9%) patients. In the univariable analysis, CTRCD was more common in the high-risk group (p = 0.005) and in patients with a CAC score greater than zero (p = 0.036). In multivariable analysis, the incidence of CTRCD remains higher in the CAC score > 0 group, even after adjusting for age, hypertension, and hyperlipidemia. In this study group, the CTRCD rates increased with the HFA-ICOS risk score. Conclusions: In moderate and high-risk patients, a coronary artery calcium score greater than zero was identified as a significant risk factor for the development of cancer therapy-related cardiac dysfunction during anthracycline-based treatment. Furthermore, the HFA-ICOS risk score demonstrated good correlation with the incidence of CTRCD in this study, supporting its validity as a predictive tool in patients receiving anthracycline therapy. Full article

Background/Objectives: Doxorubicin (DOX), a widely used anthracycline chemotherapeutic agent, is recognized for its efficacy in treating various malignancies. However, its clinical application is critically limited due to dose-dependent cardiotoxicity, predominantly induced by oxidative stress and compromised antioxidant defenses. Photobiomodulation (PBM), a non-invasive intervention that utilizes low-intensity light, has emerged as a promising therapeutic modality in regenerative medicine, demonstrating benefits such as enhanced tissue repair, reduced inflammation, and protection against oxidative damage. This investigation sought to evaluate the cardioprotective effects of PBM preconditioning in human-induced pluripotent stem cell-derived ventricular cardiomyocytes (hiPSC-vCMs) subjected to DOX-induced toxicity. Methods: Human iPSC-vCMs were allocated into three experimental groups: control cells (untreated), DOX-treated cells (exposed to 2 μM DOX for 24 h), and PBM+DOX-treated cells (preconditioned with PBM, utilizing 660 nm ±10 nm LED light at an intensity of 10 mW/cm² for 500 s, delivering an energy dose of 5 J/cm², followed by DOX exposure). Cell viability assessments were conducted in conjunction with evaluations of oxidative stress markers, including antioxidant enzyme activities and malondialdehyde (MDA) levels. Furthermore, transcriptional profiling of 40 genes implicated in cardiac dysfunction was performed using TaqMan quantitative polymerase chain reaction (qPCR), complemented by analyses of protein expression for markers of cardiac stress, inflammation, and apoptosis. Results: Exposure to DOX markedly reduced the viability of hiPSC-vCMs. The cells exhibited significant alterations in the expression of 32 out of 40 genes (80%) after DOX exposure, reflecting the upregulation of markers associated with apoptosis, inflammation, and adverse cardiac remodeling. PBM preconditioning partially restored the cell viability, modulating the expression of 20 genes (50%), effectively counteracting a substantial proportion of the dysregulation induced by DOX. Notably, PBM enhanced the expression of genes responsible for antioxidant defense, augmented antioxidant enzyme activity, and reduced oxidative stress indicators such as MDA levels. Additional benefits included downregulating stress-related mRNA markers (HSP1A1 and TNC) and apoptotic markers (BAX and TP53). PBM also demonstrated gene reprogramming effects in ventricular cells, encompassing regulatory changes in NPPA, NPPB, and MYH6. PBM reduced the protein expression levels of IL-6, TNF, and apoptotic markers in alignment with their corresponding mRNA expression profiles. Notably, PBM preconditioning showed a diminished expression of BNP, emphasizing its positive impact on mitigating cardiac stress. Conclusions: This study demonstrates that PBM preconditioning is an effective strategy for reducing DOX-induced chemotherapy-related cardiotoxicity by enhancing cell viability and modulating signaling pathways associated with oxidative stress, as well as inflammatory and hypertrophic markers. Full article

Cardiotoxicity related to anthracyclines and trastuzumab represents a significant clinical challenge in cancer therapy, often limiting treatment efficacy and patient survival. The underlying mechanisms of cardiotoxicity involve the activation of NLRP3 and the MyD88-dependent signaling pathway. Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), such as inclisiran, are known for their lipid-lowering effects, but emerging data indicate that they may also exert pleiotropic benefits beyond cholesterol reduction. This study investigates whether inclisiran can mitigate the cardiotoxic effects of anthracyclines and trastuzumab through reduction of NLRP3 activation and MyD88 signaling, independently of its effects on dyslipidemia. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were exposed to subclinical concentrations of doxorubicin (1 µM) and trastuzumab in sequential therapy (200 nM), alone or in combination with inclisiran (100 nM) for 24 h. After the incubation period, we performed the following tests: determination of cardiomyocytes apoptosis, analysis of intracellular reactive oxygen species, lipid peroxidation products (including malondialdehyde and 4-hydroxynonenal), intracellular mitofusin-2 and Ca⁺⁺ levels. Troponin and BNP were quantified through selective ELISA methods. A confocal laser scanning microscope was used to study cardiomyocyte morphology and F-actin staining after treatments. Moreover, pro-inflammatory studies were also performed, including the intracellular expression of NLRP-3, MyD-88 and twelve cytokines/growth factors involved in cardiotoxicity (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IFN-γ, TNF-α, G-CSF, GM-CSF). Inclisiran co-incubated with doxorubicin and trastuzumab exerts significant cardioprotective effects, enhancing cell viability by 88.9% compared to only DOXO/TRA treated cells (p < 0.001 for all). Significant reduction of oxidative stress, and intracellular levels of NLRP-3, MyD88, IL-1α, IL-1β, IL-6, IL-12, IL17-α, TNF-α, G-CSF were seen in the inclisiran group vs. only DOXO/TRA (p < 0.001). For the first time, PCSK9i inclisiran has been shown to exert significant anti-inflammatory effects to reduce anthracycline-HER-2 blocking agent-mediated cardiotoxicity through NLRP-3 and Myd-88 related pathways. The overall conclusions of the study warrant further investigation of the use of PCSK9i in primary prevention of CTRCD in cancer patients, independently from dyslipidemia. Full article

Anthracyclines play an irreplaceable role in cancer treatment, although their clinical application is limited due to severe side effects such as arrhythmia, cardiomyopathy, and myocardial infarction. The currently available clinical drugs for treating anthracycline-induced cardiotoxicity (AIC) are limited by numerous drawbacks, including the side effects of the therapeutic agents, single treatment mechanisms, and individual patient variations. Therefore, novel drugs with broader applicability and multitarget synergistic protective effects are, therefore, urgently needed. Ginsenosides, the primary bioactive constituents of plants belonging to the genus Panax (family Araliaceae), exhibit a wide range of pharmacological activities, including anti-inflammatory, antioxidative, and antitumor effects, and have demonstrated cardioprotective properties against AIC. This article examines the mechanisms of AIC and the modulatory effects of ginsenosides on these mechanisms. This review highlights the potential molecular targets and signaling pathways through which ginsenosides exert therapeutic effects on AIC, including the regulation of oxidative-stress-related pathways such as Keap1/Nrf2, MAPK, STAT, PI3K/Akt, and AMPK; the restoration of mitochondrial function; the modulation of autophagy; and the inhibition of pyroptosis, ferroptosis, and apoptosis. Therefore, this review serves as a theoretical basis and provides a research direction for future investigation regarding the prevention and treatment of AIC with ginsenosides, as well as clinical translation studies. Full article

Sodium–glucose cotransporter-2 inhibitors (SGLT2i), initially developed for the management of type 2 diabetes mellitus, have demonstrated significant nephroprotective and cardioprotective effects. These benefits have led to their inclusion in heart failure (HF) management guidelines, irrespective of glycemic status and left ventricular ejection fraction (LVEF). Various anticancer therapies, particularly anthracyclines, are associated with substantial cardiotoxicity risks, resulting in cancer therapy-related cardiovascular toxicity (CTR-CVT). Promising evidence from preclinical and observational studies indicates that SGLT2i may mitigate cardiotoxic effects of cancer therapy by alleviating LVEF decline, reducing HF incidence and hospitalizations, and lowering overall mortality. Moreover, improved survival has been reported in patients with various malignancies. The current review explores the potential applications of SGLT2i in the prevention of CTR-CVT, highlights their possible mechanisms of cardioprotection, discusses the published evidence, and emphasizes the need for the results from ongoing randomized controlled trials to establish SGLT2i efficacy and safety in cardio-oncology patients. Full article

Anthracyclines remain a cornerstone of cancer therapy but are associated with a significant risk of cardiotoxicity, which can lead to overt heart failure. The risk is modulated by cumulative dose, pre-existing cardiovascular disease, and patient-specific factors. As cancer survival improves, the long-term cardiovascular consequences of anthracycline exposure have become a growing concern, underscoring the need for effective preventive strategies. This narrative review examines lifestyle and pharmacological interventions aimed at mitigating anthracycline-induced cardiotoxicity. Evidence suggests that structured exercise programs and antioxidant-rich diets may enhance cardiovascular resilience, while beta-blockers, renin-angiotensin system inhibitors, and dexrazoxane remain central pharmacological options. Emerging therapies, including sodium-glucose co-transporter 2 inhibitors and sacubitril/valsartan, show promise but require further investigation. A comprehensive approach that integrates lifestyle modifications with pharmacological strategies within a multidisciplinary cardio-oncology framework may provide optimal protection, improving long-term cardiovascular outcomes in cancer patients receiving anthracyclines. Full article

Purpose: Doxorubicin (DOX) is a broad-spectrum anti-tumor anthracycline drug. However, its clinical application is greatly limited due to the side effect of cardiotoxicity. Caffeic acid phenethyl ester (CAPE) is one of the major biologically active compounds isolated from propolis, which is effective in the treatment of cardiovascular diseases. The purpose of this study aimed to explore the possible mechanism of CAPE’s protective effect on DOX-induced cardiotoxicity (DIC). Methods: In vivo, a DIC model was established by the intraperitoneal injection of 3 mg/kg DOX. The cardiac function of mice was monitored by electrocardiograms. Histopathological changes in myocardial tissue were detected by H&E staining. Serum samples were tested for the level of markers of myocardial injury. In vitro, transmission electron microscopy was used to assess the mitochondrial damage. Oxidative stress was measured by flow cytometry and mitochondrial respiration analysis. Necroptosis pathway changes were detected by Western blotting. Furthermore, the overexpression plasmid of a key necroptosis gene, necroptosis inhibitor or ROS inducer/inhibitor was applied to H9c2 and AC16 cells to explore whether CAPE exerted a protective effect against DIC through the cross-talk mediated by ROS and MLKL. Results: CAPE could improve the cardiac function and protect against myocardial tissue. CAPE pre-administration treatment attenuated the DOX-induced generation of ROS, protected mitochondrial functions and inhibited necroptosis. Moreover, there was cross-talk between the ROS and necroptosis. CAPE could protect against DIC by inhibiting the ROS-MLKL signaling that regulated the cross-talk. Conclusions: CAPE alleviated the oxidative stress and necroptosis of DIC, indicating that the cross-talk mediated by ROS-MLKL signaling may be a potential therapeutic mechanism for clinical DIC. Full article

Anthracyclines and human epidermal growth factor receptor 2 (HER-2) inhibitors are cornerstone therapies for breast cancer but are associated with significant cardiotoxicity. While sodium–glucose cotransporter 2 (SGLT2) inhibitors such as dapagliflozin have demonstrated cardio–renal protective effects during anthracycline treatment, their efficacy in preventing cardiotoxicity from sequential anthracycline and HER-2 blockade remains poorly understood. This study investigates the cardioprotective role of dapagliflozin in a preclinical model of chemotherapy-induced cardiotoxicity. Female C57Bl/6 mice were divided into four groups and treated for 10 days as follows: (1) a normal control group receiving saline (sham); (2) a model control group receiving doxorubicin (2.17 mg/kg/day for 5 days) followed by HER-2-blocking monoclonal antibody (2.25 mg/kg/day for 5 days); (3) a dapagliflozin-only group (10 mg/kg/day via oral gavage); and (4) a treatment group receiving the combination of doxorubicin, HER-2 inhibitor, and dapagliflozin. Cardiac function was assessed using echocardiography (VEVO 2100). Biomarkers of myocardial injury and inflammation (NLRP3, MyD88, CXCR4, H-FABP, troponin-T, and cytokines) were quantified via ELISA and immunohistochemistry. Circulating markers such as mitofusin-2, cardiac myosin light chain, malondialdehyde (MDA), and 4-hydroxy-2-nonenal (4-HNE) were also measured. Dapagliflozin significantly preserved the ejection fraction and reduced both radial and longitudinal strain impairment in mice treated with the doxorubicin–HER-2 inhibitor combination (p < 0.001). Levels of myocardial NLRP3, MyD88, CXCR4, H-FABP, interleukin-1β, and troponin-T were significantly lower in the dapagliflozin-treated group compared to the chemotherapy-only group. Serum markers of oxidative stress and cardiac injury, including mitofusin-2, MDA, 4-HNE, BNP, and high-sensitivity C-reactive protein (hs-CRP), were also reduced by dapagliflozin treatment. Our findings demonstrate that dapagliflozin effectively mitigates early cardiac dysfunction and injury in a preclinical model of sequential doxorubicin and HER-2 inhibitor therapy. Full article

Secondary dilated cardiomyopathy (DCM) refers to left ventricular dilation and impaired systolic function arising from identifiable extrinsic causes, such as ischemia, hypertension, toxins, infections, systemic diseases, or metabolic disorders. Unlike primary DCM, which is predominantly genetic, secondary DCM represents a diverse spectrum of pathophysiological mechanisms linked to external insults on myocardial structure and function. The increasing prevalence of conditions such as alcohol use disorder, chemotherapy-induced cardiotoxicity, and viral myocarditis underscores the need for heightened awareness and early recognition of secondary DCM. A comprehensive analysis of clinical trial data and observational studies involving secondary dilative cardiomyopathy was conducted, with a focus on mortality, symptom relief, and major adverse events. A systematic literature review was performed using databases, including PubMed, Embase, and ClinicalTrials.gov, following PRISMA guidelines for study selection. Data were extracted on patient demographics, etiology of dilation, trial design, outcomes, and follow-up duration. Advances in diagnostic modalities have refined the ability to identify underlying causes of secondary DCM. For example, high-sensitivity troponin and cardiac magnetic resonance imaging are pivotal in diagnosing myocarditis and differentiating it from ischemic cardiomyopathy. Novel insights into toxin-induced cardiomyopathies, such as those related to anthracyclines and immune checkpoint inhibitors, have highlighted pathways of mitochondrial dysfunction and oxidative stress. Treatment strategies emphasize the management of the causing condition alongside standard heart failure therapies, including RAAS inhibitors and beta-blockers. Emerging therapies, such as myocardial recovery protocols in peripartum cardiomyopathy and immune-modulating treatments in myocarditis, are promising in reversing myocardial dysfunction. Secondary DCM encompasses a heterogeneous group of disorders that require a precise etiological diagnosis for effective management. Timely identification and treatment of the underlying cause, combined with optimized heart failure therapies, can significantly improve outcomes. Future research focuses on developing targeted therapies and exploring the role of biomarkers and precision medicine in tailoring treatment strategies for secondary DCM. Full article

Breast cancer is the most common cancer in women worldwide. Anthracyclines (doxorubicin, epirubicin, daunorubicin, idarubicin) are among the most used drugs for the treatment of breast cancer. Unfortunately, anthracyclines cause cardiotoxicity, which is a limiting factor for its use, and the lifetime cumulative dose of anthracyclines is the major risk factor for cardiotoxicity. In our study, we focused on acute and subacute heart damage. One of the main factors is a genetic predisposition, which determines individual susceptibility to anthracycline cardiotoxicity. The main idea of this study was, for the first time, to evaluate drug metabolism-related genes as a risk factor for developing cardiovascular toxicity in breast cancer patients. The main objective of our study was to identify the impact of drug metabolism-related gene SNPs on the development of subclinical heart damage during and/or after doxorubicin-based chemotherapy in breast cancer patients. The data of 81 women with breast cancer treated with doxorubicin-based chemotherapy in an outpatient clinic were analyzed, and SNP RT-PCR tests were performed. The drug metabolism-related gene variants SULT2B1 rs10426377, UGT1A6 rs17863783, CBR1 rs9024, CBR3 rs1056892, NCF4 rs1883112, and CYBA rs1049255 did not reach a statistically important impact on ABCC in multivariate logistic regression analysis. However, we identified that NCF4 rs1883112 had a risk reduction tendency for ABCC (OR = 0.49, 95% CI 0.27–0.87, p = 0.015). Our findings suggest that some SNPs, such as NCF4 rs1883112, may be associated with a reduced risk of cardiotoxicity, while no variants in this study showed a statistically significant increased risk. Even though, NCF4 rs1883112 showed a risk reduction tendency, suggesting the potential for personalized risk stratification. We can conclude that multiple genes are involved in ABCC, with different impacts, and it is unlikely that there is a single driver gene in ABCC pathogenesis. Full article

Cancer medications can cause cardiac issues, which are difficult to treat in oncologic patients because of the risk of complications. In some cases, this may significantly impact their well-being and treatment outcomes. Overall, these complications fall under the term “drug induced cardiotoxicity”, mainly due to chemotherapy drugs being specifically toxic to the heart, causing a decrease in the heart’s capacity to pump blood efficiently and leading to a reduction in the left ventricular ejection fraction (LVEF), and subsequently possibly leading to heart failure. Anthracyclines, alkylating agents, and targeted therapies for cancer hold the potential of causing harmful effects on the heart. The incidence of heart-related issues varies from patient to patient and depends on multiple factors, including the type of medication, dosage, duration of the treatment, and pre-existing heart conditions. The underlying mechanism leading to oncologic-drug-induced cardiovascular harmful effects is quite complex. One particular group of drugs, called anthracyclines, have garnered attention due to their impact on oxidative stress and their ability to cause direct harm to heart muscle cells. Reactive oxygen species (ROS) cause harm by inducing damage and programmed cell death in heart cells. Conventional biomarkers alone can only indicate some degree of damage that has already occurred and, therefore, early detection is key. Novel methods like genetic profiling are being developed to detect individuals at risk, prior to the onset of clinical symptoms. Key management strategies—including early detection, personalized medicine approaches, and the use of novel biomarkers—play a crucial role in mitigating cardiotoxicity and improving patient outcomes. Identification of generated genetic alterations and the association to an increased likelihood of cardiotoxicity will allow treatment in a more personalized approach, aiming at decreasing rates of cardiac events while maintaining high oncological efficacy. Oncology drug-induced cardiotoxicity is managed through a combination of preventive strategies and therapeutic interventions from the union of cardiac and oncological knowledge. Full article

Cardiovascular–kidney–metabolic (CKM) syndrome represents a complex interplay between cardiovascular disease (CVD), chronic kidney disease (CKD), and metabolic disorders, significantly impacting cancer patients. The presence of CKM syndrome in cancer patients not only worsens their prognosis but also increases the risk of major adverse cardiovascular events (MACE), reduces quality of life (QoL), and affects overall survival (OS). Furthermore, several anticancer therapies, including anthracyclines, tyrosine kinase inhibitors, immune checkpoint inhibitors, and hormonal treatments, can exacerbate CKM syndrome by inducing cardiotoxicity, nephrotoxicity, and metabolic dysregulation. This review explores the pathophysiology of CKM syndrome in cancer patients and highlights emerging therapeutic strategies to mitigate its impact. We discuss the role of novel pharmacological interventions, including sodium-glucose cotransporter-2 inhibitors (SGLT2i), proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), and soluble guanylate cyclase (sGC) activators, as well as dietary and lifestyle interventions. Optimizing the management of CKM syndrome in cancer patients is crucial to improving OS, enhancing QoL, and reducing MACE. By integrating cardiometabolic therapies into oncologic care, we can create a more comprehensive treatment approach that reduces the burden of cardiovascular and renal complications in this vulnerable population. Further research is needed to establish personalized strategies for CKM syndrome prevention and treatment in cancer patients. Full article

Chemotherapeutic agents play a crucial role in cancer treatment. However, their use is often associated with significant adverse effects, particularly cardiotoxicity. Drugs such as anthracyclines (e.g., doxorubicin) and platinum-based agents (e.g., cisplatin) cause mitochondrial damage, which is one of the main mechanisms underlying cardiotoxicity. These drugs induce oxidative stress, leading to an increase in reactive oxygen species (ROS), which in turn damage the mitochondria in cardiomyocytes, resulting in impaired cardiac function and heart failure. Mitochondria-targeted antioxidants (MTAs) have emerged as a promising cardioprotective strategy, offering a potential solution. These agents efficiently scavenge ROS within the mitochondria, protecting cardiomyocytes from oxidative damage. Recent studies have shown that MTAs, such as elamipretide, SkQ1, CoQ10, and melatonin, significantly mitigate chemotherapy-induced cardiotoxicity. These antioxidants not only reduce oxidative damage but also help maintain mitochondrial structure and function, stabilize mitochondrial membrane potential, and prevent excessive opening of the mitochondrial permeability transition pore, thus preventing apoptosis and cardiac dysfunction. In this review, we integrate recent findings to elucidate the mechanisms of chemotherapy-induced cardiotoxicity and highlight the substantial therapeutic potential of MTAs in reducing chemotherapy-induced heart damage. These agents are expected to offer safer and more effective treatment options for cancer patients in clinical practice. Full article

Anthracyclines are a class of chemotherapeutics commonly used to treat a range of cancers. Despite success in improving cancer survival rates, anthracyclines have dose-limiting cardiotoxicity that prevents more widespread clinical utility. Currently, the therapeutic options for these patients are limited to the iron-chelating agent dexrazoxane, the only FDA-approved drug for anthracycline cardiotoxicity. However, the clinical use of dexrazoxane has failed to replicate expectations from preclinical studies. A limited list of GPCRs have been identified as pathogenic in anthracycline-induced cardiotoxicity, including receptors (frizzled, adrenoreceptors, angiotensin II receptors) previously implicated in cardiac remodeling in other pathologies. The RNA sequencing of iPSC-derived cardiac myocytes from patients has increased our understanding of the pathogenic mechanisms driving cardiotoxicity. These data identified changes in the expression of novel GPCRs, heterotrimeric G proteins, and the regulatory pathways that govern downstream signaling. This review will capitalize on insights from these experiments to explain aspects of disease pathogenesis and cardiac remodeling. These data provide a cornucopia of possible unexplored potential pathways by which we can reduce the cardiotoxic side effects, without compromising the anti-cancer effects, of doxorubicin and provide new therapeutic options to improve the recovery and quality of life for patients undergoing chemotherapy. Full article