ABSTRACT

Human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC) is a highly aggressive subtype associated with poor prognosis. The advent of HER2-targeted drugs, including monoclonal antibodies, tyrosine-kinase inhibitors (TKIs) and antibody-drug conjugates, has yielded improved prognosis for patients. Compared with widely used monoclonal antibodies, small-molecule TKIs have unique advantages including oral administration and favorable penetration of blood-brain barrier for brain metastatic BC, and reduced cardiotoxicity. Pyrotinib is an irreversible TKI of the pan-ErbB receptor, and has recently been shown to be clinically effective for the treatment of HER2-positive BC in metastatic and neoadjuvant settings. This review highlights the development on the application of pyrotinib-based therapeutic approaches in the clinical settings of HER2-positive BC.

PMID:37789330 | PMC:PMC10546716 | DOI:10.1186/s13058-023-01694-5

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PubMed articles on: Cardio-Oncology

Fabrication of blended nanofibrous cardiac patch transplanted with TGF-β3 and human umbilical cord MSCs-derived exosomes for potential cardiac regeneration after acute myocardial infarction

Nanomedicine. 2023 Oct 1:102708. doi: 10.1016/j.nano.2023.102708. Online ahead of print.

ABSTRACT

Acute myocardial infarction (AMI) is a common cardiovascular condition that progressively results in heart failure. In the present study, we have designed to load transforming growth factor beta 3 (TGF-β3) and cardio potential exosomes into the blended polycaprolactone/type I collagen (PCL/COL-1) nanofibrous patch (Exo@TGF-β3@NFs) and examined its feasibility for cardiac repair. The bioactivity of the developed NFs towards the migration and proliferation of human umbilical vein endothelial cells was determined using in vitro cell compatibility assays. Additionally, Exo@TGF-β3/NFs showed up-regulation of genes involved in angiogenesis and mesenchymal differentiations in vitro. The in vivo experiments performed 4 weeks after transplantation showed that the Exo@TGF-β3@NFs had a higher LV ejection fraction and fraction shortening functions. Subsequently, it has been determined that Exo@TGF-β3@NFs significantly reduced AMI size and fibrosis and increased scar thickness. The developed NFs approach will become a useful therapeutic approach for the treatment of AMI.

PMID:37788793 | DOI:10.1016/j.nano.2023.102708

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PubMed articles on: Cardio-Oncology

Anthracycline Toxicity: Light at the End of the Tunnel?

Annu Rev Pharmacol Toxicol. 2023 Oct 3. doi: 10.1146/annurev-pharmtox-022823-035521. Online ahead of print.

ABSTRACT

Anthracycline-induced cardiotoxicity (AIC) is a serious and common side effect of anthracycline therapy. Identification of genes and genetic variants associated with AIC risk has clinical potential as a cardiotoxicity predictive tool and to allow the development of personalized therapies. In this review, we provide an overview of the function of known AIC genes identified by association studies and categorize them based on their mechanistic implication in AIC. We also discuss the importance of functional validation of AIC-associated variants in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to advance the implementation of genetic predictive biomarkers. Finally, we review how patient-specific hiPSC-CMs can be used to identify novel patient-relevant functional targets and for the discovery of cardioprotectant drugs to prevent AIC. Implementation of functional validation and use of hiPSC-CMs for drug discovery will identify the next generation of highly effective and personalized cardioprotectants and accelerate the inclusion of approved AIC biomarkers into clinical practice. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 64 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

PMID:37788492 | DOI:10.1146/annurev-pharmtox-022823-035521

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PubMed articles on: Cardio-Oncology

Cancer survivorship at heart: a multidisciplinary cardio-oncology roadmap for healthcare professionals

Front Cardiovasc Med. 2023 Sep 15;10:1223660. doi: 10.3389/fcvm.2023.1223660. eCollection 2023.

ABSTRACT

In cancer, a patient is considered a survivor from the time of initial diagnosis until the end of life. With improvements in early diagnosis and treatment, the number of cancer survivors (CS) has grown considerably and includes: (1) Patients cured and free from cancer who may be at risk of late-onset cancer therapy-related cardiovascular toxicity (CTR-CVT); (2) Patients with long-term control of not-curable cancers in whom CTR-CVT may need to be addressed. This paper highlights the importance of the cancer care continuum, of a patient-centered approach and of a prevention-oriented policy. The ultimate goal is a personalized care of CS, achievable only through a multidisciplinary-guided survivorship care plan, one that replaces the fragmented management of current healthcare systems. Collaboration between oncologists and cardiologists is the pillar of a framework in which primary care providers and other specialists must be engaged and in which familial, social and environmental factors are also taken into account.

PMID:37786510 | PMC:PMC10541962 | DOI:10.3389/fcvm.2023.1223660

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PubMed articles on: Cardio-Oncology

Premature senescence and cardiovascular disease following cancer treatments: mechanistic insights

Front Cardiovasc Med. 2023 Sep 14;10:1212174. doi: 10.3389/fcvm.2023.1212174. eCollection 2023.

ABSTRACT

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality, especially among the aging population. The "response-to-injury" model proposed by Dr. Russell Ross in 1999 emphasizes inflammation as a critical factor in atherosclerosis development, with atherosclerotic plaques forming due to endothelial cell (EC) injury, followed by myeloid cell adhesion and invasion into the blood vessel walls. Recent evidence indicates that cancer and its treatments can lead to long-term complications, including CVD. Cellular senescence, a hallmark of aging, is implicated in CVD pathogenesis, particularly in cancer survivors. However, the precise mechanisms linking premature senescence to CVD in cancer survivors remain poorly understood. This article aims to provide mechanistic insights into this association and propose future directions to better comprehend this complex interplay.

PMID:37781317 | PMC:PMC10540075 | DOI:10.3389/fcvm.2023.1212174

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PubMed articles on: Cardio-Oncology

The broad spectrum of cardiotoxicities from immunotherapies

Front Cardiovasc Med. 2023 Sep 15;10:1259620. doi: 10.3389/fcvm.2023.1259620. eCollection 2023.

NO ABSTRACT

PMID:37781307 | PMC:PMC10540439 | DOI:10.3389/fcvm.2023.1259620

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PubMed articles on: Cardio-Oncology

Approaches for reducing chemo/radiation-induced cardiotoxicity by nanoparticles

Environ Res. 2023 Sep 28:117264. doi: 10.1016/j.envres.2023.117264. Online ahead of print.

ABSTRACT

Nanoparticles are fascinating and encouraging carriers for cancer treatment due to their extraordinary properties and potential applications in targeted drug delivery, treatment, and diagnosis. Experimental studies including in vitro and in vivo examinations show that nanoparticles can cause a revolution in different aspects of cancer therapy. Normal tissue toxicity and early and late consequences are the major limitations of cancer therapy by radiotherapy and chemotherapy. However, the delivery of drugs into tumors or reducing the accumulation of drugs in normal tissues can permit a more satisfactory response of malignancies to therapy with more inferior side effects. Cardiac toxicity is one of the major problems for chemotherapy and radiotherapy. Therefore, several experimental studies have been performed to minimize the degenerative impacts of cancer treatment on the heart and also enhance the influences of radiotherapy and chemotherapy agents in cancers. This review article emphasizes the benefits of nanoparticle-based drug delivery techniques, including minimizing the exposure of the heart to anticancer drugs, enhancing the accumulation of drugs in cancers, and expanding the effectiveness of radiotherapy. The article also discusses the challenges and problems accompanied with nanoparticle-based drug delivery techniques such as toxicity, which need to be addressed through further research. Moreover, the article emphasizes the importance of developing safe and effective nanoparticle-based therapies that can be translated into clinical practice.

PMID:37776941 | DOI:10.1016/j.envres.2023.117264

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PubMed articles on: Cardio-Oncology

Utilizing coordination chemistry through formation of a CuII-quinalizarin complex to manipulate cell biology: An in vitro, in silico approach

J Inorg Biochem. 2023 Sep 21;249:112369. doi: 10.1016/j.jinorgbio.2023.112369. Online ahead of print.