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11/16/25

ABSTRACT

Microtubule polymerization inhibitors (MPIs) have long been used as anticancer agents because they inhibit mitosis. Microtubules are thought to play an important role in the migration of tumor cells and the formation of tumor blood vessels, and new MPIs are being developed. Many clinical trials of novel MPIs have been conducted in humans, while some clinical studies in dogs have also been reported. More attempts to apply MPIs not only in humans but also in the veterinary field are expected to be made in the future. Meanwhile, MPIs have a risk of cardiotoxicity. In this paper, we review findings on the pharmacological effects and cardiotoxicity of MPIs, as well as the mechanisms of their cardiotoxicity. Cardiotoxicity of MPIs involves not only the direct effects of MPIs on cardiomyocytes but also their effects on vascular function. For example, hypertension induced by impaired vascular function also contributes to the exacerbation of myocardial damage, and blood pressure control may be useful in reducing cardiotoxicity. By combined administration of MPIs and other anticancer agents, MPI efficacy may be enhanced, thereby potentially allowing to keep MPI dosage low. Measurement of myocardial injury markers in blood and echocardiography may be useful for monitoring cardiotoxicity. In particular, two-dimensional speckle tracking may have high sensitivity for the early detection of MPI-induced cardiac dysfunction. The exploration of the potential of new MPIs while understanding their toxicity and how to deal with them will lead to the further development of cancer chemotherapy.

PMID:37496236 | DOI:10.1002/jat.4521

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PubMed articles on: Cardio-Oncology

Radiotherapy-induced diffuse myocardial fibrosis in early-stage breast cancer patients - multimodality imaging study with six-year follow-up

Radiat Oncol. 2023 Jul 26;18(1):124. doi: 10.1186/s13014-023-02319-z.

ABSTRACT

BACKGROUND: Breast radiotherapy (RT) induces diffuse myocardial changes, which may increase the incidence of heart failure with preserved ejection fraction. This study aimed to evaluate the early signs of diffuse fibrosis after RT and their evolution during a six-year follow-up.

METHODS: Thirty patients with early-stage left-sided breast cancer were studied with echocardiography and electrocardiography (ECG) at baseline, after RT, and at three-year and six-year follow-up visits. Echocardiography analysis included an off-line analysis of integrated backscatter (IBS). ECG was analysed for fragmented QRS (fQRS). In addition, cardiac magnetic resonance (CMR) imaging was performed at the six-year control. The left ventricle 16-segment model was used in cardiac imaging, and respective local radiation doses were analysed.

RESULTS: Regional myocardial reflectivity in inferoseptal segments increased by 2.02 (4.53) dB (p = 0.026) and the percentage of leads with fQRS increased from 9.2 to 16.4% (p = 0.002) during the follow-up. In CMR imaging, abnormal extracellular volume (ECV) and T1 mapping values were found with anteroseptal and apical localization in a median of 3.5 (1.00-5.75) and 3 (1.25-4.00) segments, respectively. A higher left ventricle radiation dose was associated with an increased likelihood of having changes simultaneously in CMR and echocardiography (OR 1.26, 95% Cl. 1.00-1.59, p = 0.047).

CONCLUSIONS: After radiotherapy, progressive changes in markers of diffuse myocardial fibrosis were observed in a multimodal manner in ECG and echocardiography. Changes in echocardiography and abnormal values in CMR were localized in the septal and apical regions, and multiple changes were associated with higher radiation doses.

PMID:37496091 | DOI:10.1186/s13014-023-02319-z

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PubMed articles on: Cardio-Oncology

Molecular basis of GDF15 induction and suppression by drugs in cardiomyocytes and cancer cells toward precision medicine

Sci Rep. 2023 Jul 26;13(1):12061. doi: 10.1038/s41598-023-38450-w.

ABSTRACT

GDF15 has recently emerged as a key driver of the development of various disease conditions including cancer cachexia. Not only the tumor itself but also adverse effects of chemotherapy have been reported to contribute to increased GDF15. Although regulation of GDF15 transcription by BET domain has recently been reported, the molecular mechanisms of GDF15 gene regulation by drugs are still unknown, leaving uncertainty about the safe and effective therapeutic strategies targeting GDF15. We screened various cardiotoxic drugs and BET inhibitors for their effects on GDF15 regulation in human cardiomyocytes and cancer cell lines and analyzed in-house and public gene signature databases. We found that DNA damaging drugs induce GDF15 in cardiomyocytes more strongly than drugs with other modes of action. In cancer cells, GDF15 induction varied depending on drug- and cell type-specific gene signatures including mutations in PI3KCA, TP53, BRAF and MUC16. GDF15 suppression by BET inhibition is particularly effective in cancer cells with low activity of the PI3K/Akt axis and high extracellular concentrations of pantothenate. Our findings provide insights that the risk for GDF15 overexpression and concomitant cachexia can be reduced by a personalized selection of anticancer drugs and patients for precision medicine.

PMID:37495707 | DOI:10.1038/s41598-023-38450-w

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PubMed articles on: Cardio-Oncology

Cardio-oncology: Shared Genetic, Metabolic, and Pharmacologic Mechanism

Curr Cardiol Rep. 2023 Jul 26. doi: 10.1007/s11886-023-01906-6. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: The article aims to investigate the complex relationship between cancer and cardiovascular disease (CVD), with a focus on the effects of cancer treatment on cardiac health.

RECENT FINDINGS: Advances in cancer treatment have improved long-term survival rates, but CVD has emerged as a leading cause of morbidity and mortality in cancer patients. The interplay between cancer itself, treatment methods, homeostatic changes, and lifestyle modifications contributes to this comorbidity. Recent research in the field of cardio-oncology has revealed common genetic mutations, risk factors, and metabolic features associated with the co-occurrence of cancer and CVD. This article provides a comprehensive review of the latest research in cardio-oncology, including common genetic mutations, risk factors, and metabolic features, and explores the interactions between cancer treatment and CVD drugs, proposing novel approaches for the management of cancer and CVD.

PMID:37493874 | DOI:10.1007/s11886-023-01906-6

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PubMed articles on: Cardio-Oncology

Multimodality imaging in cardio-oncology: the added value of CMR and CCTA

Br J Radiol. 2023 Jul 26:20220999. doi: 10.1259/bjr.20220999. Online ahead of print.

ABSTRACT

During the last 30 years, we have assisted to a great implementation in anticancer treatment with a subsequent increase of cancer survivors and decreased mortality. This has led to an ongoing interest about the possible therapy-related side-effects and their management to better guide patients therapy and surveillance in the chronic and long-term setting. As a consequence cardio-oncology was born, involving several different specialties, among which radiology plays a relevant role. Till the end of August 2022, when European Society of Cardiology (ESC) developed the first guidelines on cardio-oncology, no general indications existed to guide diagnosis and treatment of cancer therapy-related cardiovascular toxicity (CTR-CVT). They defined multimodality imaging role in primary and secondary prevention strategies, cancer treatment surveillance and early CTR-CVT identification and management.Cardiac computed tomography angiography (CCTA) has acquired a central role in coronary assessment, as far as coronary artery disease (CAD) exclusion is concerned; but on the side of this well-known application, it also started to be considered in left ventricular function evaluation, interstitial fibrosis quantification and cardiac perfusion studies.Cardiac magnetic resonance (CMR), instead, has been acknowledged as the gold standard alternative to trans-thoracic echocardiography (TTE) poor acoustic window in quantification of heart function and strain modifications, as well as pre- and post-contrast tissue characterization by means of T1-T2 mapping, early Gadolinium enhancement (EGE), late Gadolinium enhancement (LGE) and extracellular volume (ECV) evaluation.Our review is intended to provide a focus on the actual role of CMR and CCTA in the setting of a better understanding of cardiotoxicity and to draw some possible future directions of cardiac imaging in this field, starting from the recently published ESC guidelines.

PMID:37493228 | DOI:10.1259/bjr.20220999

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PubMed articles on: Cardio-Oncology

Penpulimab-induced complete atrioventricular block in a patient with metastatic renal cancer

HeartRhythm Case Rep. 2023 Apr 23;9(7):451-455. doi: 10.1016/j.hrcr.2023.04.007. eCollection 2023 Jul.

NO ABSTRACT

PMID:37492041 | PMC:PMC10363469 | DOI:10.1016/j.hrcr.2023.04.007

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PubMed articles on: Cardio-Oncology

Approaches to Prevent and Manage Cardiovascular Disease in Patients Receiving Therapy for Prostate Cancer

Curr Cardiol Rep. 2023 Jul 25. doi: 10.1007/s11886-023-01909-3. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Prostate cancer (PCa) is amongst the most common cancers in men worldwide. Cardiovascular (CV) risk factors and CV disease (CVD) are common comorbidities in this patient population, posing a challenge for PCa-directed therapies which can cause or worsen CVRFs and CVDs. Herein, we summarize the approaches to prevent and manage CVD in patients with PCa receiving therapy.

RECENT FINDINGS: While patients with locally advanced and metastatic PCa benefit from hormonal therapy, these treatments can potentially cause CV toxicity. Androgen receptor targeting therapies, such as androgen deprivation therapy (ADT), can induce metabolic changes and directly impact cardiovascular function, thereby reducing cardiorespiratory fitness and increasing CV mortality. Moreover, more than half of the PCa patients have poorly controlled CV risk factors at baseline. Hence, there is an urgent need to address gaps in preventing and managing CVD in PCa patients. Screening and optimizing CV risk factors and CVD in patients undergoing ADT are essential to reduce CV mortality, the leading non-cancer cause of death in PCa survivors. The risk of CV morbidity and mortality can be further mitigated by considering the patient's cardiovascular risk profile when deciding the choice and duration of ADT. A multidisciplinary team-based approach is crucial to achieve the best outcomes for PCa patients undergoing therapy.

PMID:37490155 | DOI:10.1007/s11886-023-01909-3

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PubMed articles on: Cardio-Oncology

Identification and protection of early cardiotoxicity in acute myeloid leukemia patients undergoing transplantation

Hematology. 2023 Dec;28(1):2239569. doi: 10.1080/16078454.2023.2239569.

ABSTRACT

Cardiotoxicity of antitumor therapy results in declining survival rates. More specifically, cardiotoxicity is positively correlated with cumulative dose of anthracyclines and eventually develops from reversible to irreversible. In this context, early monitoring methods should be explored for the timely detection of cardiotoxicity and cardioprotective therapy should be performed in patients under consideration for potentially cardiotoxic therapy. This paper reports a 22-year-old male patient with acute myeloid leukemia who underwent whole-course cardiac monitoring after receiving antileukemia therapy. After the early detection of an asymptomatic decrease in left ventricular ejection fraction (LVEF), along with a significant decrease in global longitudinal strain (GLS), the patient was treated with sacubitril/valsartan (Sac/Val). Finally, the patient completed four courses of chemotherapy and subsequent hematopoietic stem cell transplantation as planned. The measurements of LVEF and GLS also recovered after 2 months treatment of Sac/Val. Therefore, the early identification and protection of patients with cardiotoxicity are of paramount importance and future prospective studies are expected to develop the management and treatment of cancer treatment-related cardiac dysfunction.

PMID:37489927 | DOI:10.1080/16078454.2023.2239569

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PubMed articles on: Cardio-Oncology

DoxoDB: A Database for the Expression Analysis of Doxorubicin-Induced lncRNA Genes

Noncoding RNA. 2023 Jul 13;9(4):39. doi: 10.3390/ncrna9040039.

ABSTRACT

Cancer and cardiovascular disease are the leading causes of death worldwide. Recent evidence suggests that these two life-threatening diseases share several features in disease progression, such as angiogenesis, fibrosis, and immune responses. This has led to the emergence of a new field called cardio-oncology. Doxorubicin is a chemotherapy drug widely used to treat cancer, such as bladder and breast cancer. However, this drug causes serious side effects, including acute ventricular dysfunction, cardiomyopathy, and heart failure. Based on this evidence, we hypothesize that comparing the expression profiles of cells and tissues treated with doxorubicin may yield new insights into the adverse effects of the drug on cellular activities. To test this hypothesis, we analyzed published RNA sequencing (RNA-seq) data from doxorubicin-treated cells to identify commonly differentially expressed genes, including long non-coding RNAs (lncRNAs) as they are known to be dysregulated in diseased tissues and cells. From our systematic analysis, we identified several doxorubicin-induced genes. To confirm these findings, we treated human cardiac fibroblasts with doxorubicin to record expression changes in the selected doxorubicin-induced genes and performed a loss-of-function experiment of the lncRNA MAP3K4-AS1. To further disseminate the analyzed data, we built the web database DoxoDB.

PMID:37489459 | PMC:PMC10366827 | DOI:10.3390/ncrna9040039