ABSTRACT

Arsenic trioxide is a first-line treatment drug for acute promyelocytic leukemia, which is also effective for other kinds of leukemia. Its side effects, however, limit its clinical application, especially for patients with complex leukemia symptoms. Combination therapy can effectively alleviate these problems. This review summarizes the research progress on the combination of arsenic trioxide with anticancer drugs, vitamin and vitamin analogs, plant products, and other kinds of drugs in the treatment of leukemia. Additionally, the new progress in arsenic trioxide-induced cardiotoxicity was summarized. This review aims to provide new insights for the rational clinical application of arsenic trioxide.

PMID:37500645 | PMC:PMC10374529 | DOI:10.1038/s41420-023-01558-z

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PubMed articles on: Cardio-Oncology

Oral Oncolytics and Cardiovascular Risk Management and Monitoring

J Cardiovasc Pharmacol. 2023 Jul 27. doi: 10.1097/FJC.0000000000001458. Online ahead of print.

ABSTRACT

Oral oncolytic treatment options have expanded over the last decade and have brought to light the need to monitor and manage cardiovascular (CV) disease in patients being treated with these therapies. There is a need to assess CV risk before patients receive oral oncolytic therapy with known potential to cause negative CV sequelae such as left ventricular dysfunction, hypercholesterolemia, hypertension, and arrhythmias. The review highlights the need to evaluate traditional CV risk factors and their association with the development and progression of cancer. Additionally, this review suggests approaches to monitor for CV adverse events and manage CV disease during and after treatment with oral oncolytic therapy. Key guideline recommendations are reviewed and highlight specific approaches to minimize CV harm for patients exposed to oral oncolytic therapy. Careful monitoring and patient-centered decision making is key in choosing appropriate therapies. A multidisciplinary approach between oncologists, cardio-oncologists, pharmacists, and other members of the healthcare team is essential in navigating cardiac toxicities.

PMID:37499057 | DOI:10.1097/FJC.0000000000001458

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PubMed articles on: Cardio-Oncology

Diagnosis and Management of Cardiovascular Effects of Bruton's Tyrosine Kinase Inhibitors

Curr Cardiol Rep. 2023 Jul 27. doi: 10.1007/s11886-023-01916-4. Online ahead of print.

ABSTRACT

PURPOSE OF REVIEW: Bruton's tyrosine kinase inhibitors (BTKis) have changed the treatment and prognosis of several B-cell malignancies. However, since the approval of the first BTKi, ibrutinib, reports of cardiovascular adverse events especially atrial fibrillation have arisen. In this review, we discuss the cardiovascular side effects of BTKis and the management of these toxicities in clinical practice.

RECENT FINDINGS: BTKIs increase the risks of atrial fibrillation, bleeding, hypertension, heart failure, and potentially ventricular arrhythmia. Newer second and third-generation BTKis appear to have a lower risk of cardiovascular adverse events; however, long-term follow-up data are not available for these new BTKis. BTKis are an effective treatment for some B-cell malignancies; however, they can cause cardiovascular side effects. The best preventive strategies to minimize cardiovascular complications remain undefined. Currently, a practical approach for managing patients receiving BTKis includes the management of cardiovascular risk factors and side effects of BTKis to prevent interruption of cancer treatment.

PMID:37498449 | DOI:10.1007/s11886-023-01916-4

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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 | PMC:PMC10373367 | DOI:10.1186/s13014-023-02319-z

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PubMed articles on: Cardio-Oncology

Anti-tumor and cardiotoxic effects of microtubule polymerization inhibitors: The mechanisms and management strategies

J Appl Toxicol. 2023 Jul 26. doi: 10.1002/jat.4521. Online ahead of print.

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

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 | PMC:PMC10372009 | 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 Aug;25(8):863-878. doi: 10.1007/s11886-023-01906-6. Epub 2023 Jul 26.

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 Aug;25(8):889-899. doi: 10.1007/s11886-023-01909-3. Epub 2023 Jul 25.