Human In Vitro Models for Assessing the Genomic Basis of Chemotherapy-Induced Cardiovascular Toxicity

Pinheiro, Emily; Magdy, Tarek; Burridge, Paul W.

doi:10.1007/s12265-020-09962-x

Cited by 12 publications

(7 citation statements)

References 115 publications

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“…This allows clinicians to screen patients for susceptibility variants prior to treatment and select an alternative treatment or co-administer protective adjuvant therapy or development modified chemotherapeutics that bypass off-target pathways. Candidate gene association studies (CGAS) in which frequencies of genetic variants, mainly single nucleotide polymorphisms (SNPs) are compared between cases and controls, and genome-wide association studies (GWAS), in which genetic variations across the whole genome are analyzed, are 2 widely used methods to identify variants that may contribute to drug-specific risk factors (Pinheiro et al, 2020). However, while these studies help identify numerous genetic variants, they need further validations in order to determine the causal relationship between genetic variants and occurrence of cardiotoxicities, which is essential for further development of protective therapy (Knowles et al, 2018).…”

Section: Pharmacogenomics and Gene Polymorphism Of Anticancer Therapiesmentioning

confidence: 99%

Human Pluripotent Stem Cells for Modeling of Anticancer Therapy-Induced Cardiotoxicity and Cardioprotective Drug Discovery

Keung

Cheung

2021

Front. Pharmacol.

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Anticancer chemotherapies have been shown to produce severe side effects, with cardiotoxicity from anthracycline being the most notable. Identifying risk factors for anticancer therapy-induced cardiotoxicity in cancer patients as well as understanding its underlying mechanism is essential to improving clinical outcomes of chemotherapy treatment regimens. Moreover, cardioprotective agents against anticancer therapy-induced cardiotoxicity are scarce. Human induced pluripotent stem cell technology offers an attractive platform for validation of potential single nucleotide polymorphism with increased risk for cardiotoxicity. Successful validation of risk factors and mechanism of cardiotoxicity would aid the development of such platform for novel drug discovery and facilitate the practice of personalized medicine.

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Section: Pharmacogenomics and Gene Polymorphism Of Anticancer Therapiesmentioning

confidence: 99%

Human Pluripotent Stem Cells for Modeling of Anticancer Therapy-Induced Cardiotoxicity and Cardioprotective Drug Discovery

Keung

Cheung

2021

Front. Pharmacol.

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“…In addition to retrospective genetic analysis, the advent of human-induced pluripotent stem cell models will provide an in vitro system to explore the effect of genomic findings. This will drive hypotheses relating to the underlying mechanisms driving cardiotoxicity and will facilitate the development and investigation of novel strategies to mitigate cardiovascular toxicity [ 87 , 88 ].…”

Section: The Role Of Precision Medicinementioning

confidence: 99%

Cardiotoxicity and Chemotherapy—The Role of Precision Medicine

et al. 2021

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Cancer and cardiovascular disease are the leading causes of death in the United Kingdom. Many systemic anticancer treatments are associated with short- and long-term cardiotoxicity. With improving cancer survival and an ageing population, identifying those patients at the greatest risk of cardiotoxicity from their cancer treatment is becoming a research priority and has led to a new subspecialty: cardio-oncology. In this concise review article, we discuss cardiotoxicity and systemic anticancer therapy, with a focus on chemotherapy. We also discuss the challenge of identifying those at risk and the role of precision medicine as we strive for a personalised approach to this clinical scenario.

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“…In this context, the rapid evolution of human pluripotent stem cell (hPSC) technology, that includes embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs), provides an opportunity to generate various biologically relevant human disease models in vitro. [11][12][13] This approach has been largely favored due to its advantage in high-throughput drug screening, and its ability to faithfully recapitulate non-genetic and genetic human diseases in pathology phenotypes. 13 The advantages and limitations of 2D human cardiac disease models hPSC derived cardiomyocytes (hPSC-CMs) have shown their potential as in vitro model of human cardiac diseases.…”

Section: Introductionmentioning

confidence: 99%

Generating 3D human cardiac constructs from pluripotent stem cells

Liu

Feng

et al. 2022

eBioMedicine

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Human pluripotent stem cell (hPSC) technology has offered nearly infinite opportunities to model all kinds of human diseases in vitro. Cardiomyocytes derived from hPSCs have proved to be efficient tools for cardiac disease modeling, drug screening and pathological mechanism studies. In this review, we discuss the advantages and limitations of 2D hPSC-cardiomyocyte (hPSC-CM) system, and introduce the recent development of three-dimensional (3D) culture platforms derived from hPSCs. Although the development of bioengineering technologies has greatly improved 3D platform construction, there are certainly challenges and room for development for further in-depth research.

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Human In Vitro Models for Assessing the Genomic Basis of Chemotherapy-Induced Cardiovascular Toxicity

Cited by 12 publications

References 115 publications

Human Pluripotent Stem Cells for Modeling of Anticancer Therapy-Induced Cardiotoxicity and Cardioprotective Drug Discovery

Human Pluripotent Stem Cells for Modeling of Anticancer Therapy-Induced Cardiotoxicity and Cardioprotective Drug Discovery

Cardiotoxicity and Chemotherapy—The Role of Precision Medicine

Generating 3D human cardiac constructs from pluripotent stem cells

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