In Vivo Murine Models of Cardiotoxicity Due to Anticancer Drugs: Challenges and Opportunities for Clinical Translation

doi:10.1007/s12265-022-10231-2

Review

. 2022 Oct;15(5):1143-1162.

doi: 10.1007/s12265-022-10231-2. Epub 2022 Mar 21.

In Vivo Murine Models of Cardiotoxicity Due to Anticancer Drugs: Challenges and Opportunities for Clinical Translation

Serena L'Abbate¹, Michela Chianca¹, Iacopo Fabiani², Annamaria Del Franco^{1

3}, Alberto Giannoni^{1

3}, Giuseppe Vergaro^{1

3}, Chrysanthos Grigoratos³, Claudia Kusmic⁴, Claudio Passino^{1

3}, Yuri D'Alessandra⁵, Silvia Burchielli⁶, Michele Emdin^{1

3}, Daniela Maria Cardinale⁷

Affiliations

¹ Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
² Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy. iacopofabiani@gmail.com.
³ Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
⁴ Institute of Clinical Physiology, CNR, Pisa, Italy.
⁵ Cardiovascular Proteomics Unit, Centro Cardiologico Monzino I.R.C.C.S., Milan, Italy.
⁶ Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
⁷ Cardioncology Unit, Cardiology Division, European Institute of Oncology, I.R.C.C.S., Milan, Italy.

PMID: 35312959
DOI: 10.1007/s12265-022-10231-2

Review

In Vivo Murine Models of Cardiotoxicity Due to Anticancer Drugs: Challenges and Opportunities for Clinical Translation

Serena L'Abbate et al. J Cardiovasc Transl Res. 2022 Oct.

. 2022 Oct;15(5):1143-1162.

doi: 10.1007/s12265-022-10231-2. Epub 2022 Mar 21.

Authors

Affiliations

¹ Institute of Life Sciences, Scuola Superiore Sant'Anna, Pisa, Italy.
² Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy. iacopofabiani@gmail.com.
³ Cardiology Division, Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
⁴ Institute of Clinical Physiology, CNR, Pisa, Italy.
⁵ Cardiovascular Proteomics Unit, Centro Cardiologico Monzino I.R.C.C.S., Milan, Italy.
⁶ Fondazione Toscana Gabriele Monasterio, Pisa, Italy.
⁷ Cardioncology Unit, Cardiology Division, European Institute of Oncology, I.R.C.C.S., Milan, Italy.

PMID: 35312959
DOI: 10.1007/s12265-022-10231-2

Abstract

Modern therapeutic approaches have led to an improvement in the chances of surviving a diagnosis of cancer. However, this may come with side effects, with patients experiencing adverse cardiovascular events or exacerbation of underlying cardiovascular disease related to their cancer treatment. Rodent models of chemotherapy-induced cardiotoxicity are useful to define pathophysiological mechanisms of cardiac damage and to identify potential therapeutic targets. The key mechanisms involved in cardiotoxicity induced by specific different antineoplastic agents are summarized in this state-of-the-art review, as well as the rodent models of cardiotoxicity by different classes of anticancer drugs, along with the strategies tested for primary and secondary cardioprotection. Current approaches for early detection of cardiotoxicity in preclinical studies with a focus on the application of advanced imaging modalities and biomarker strategies are also discussed. Potential applications of cardiotoxicity modelling in rodents are illustrated in relation to the advancements of promising research topics of cardiotoxicity. Created with BioRender.com.

Keywords: Cardiac biomarker; Cardioprotection; Cardiotoxic; Chemotherapy; Rodent model; Ventricular function.

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References

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1. Curigliano, G., Cardinale, D., Suter, T., Plataniotis, G., De Azambuja, E., Sandri, M. T., et al. (2012). Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO clinical practice guidelines. Annals of Oncology, 23(SUPPL. 7). https://doi.org/10.1093/annonc/mds293
1. Li, D. L., Wang, Z. V., Ding, G., Tan, W., Luo, X., Criollo, A., et al. (2016). Doxorubicin blocks cardiomyocyte autophagic flux by inhibiting lysosome acidification. Circulation, 133(17), 1668–1687. https://doi.org/10.1161/CIRCULATIONAHA.115.017443 - DOI - PubMed - PMC
1. Asnani, A., Moslehi, J. J., Adhikari, B. B., Baik, A. H., Beyer, A. M., De Boer, R. A., et al. (2021). Preclinical models of cancer therapy-associated cardiovascular toxicity: A scientific statement from the American Heart Association. Circulation Research. https://doi.org/10.1161/RES.0000000000000473 - DOI - PubMed - PMC
1. Latifi, Y., Moccetti, F., Wu, M., Xie, A., Packwood, W., Qi, Y., et al. (2019). Thrombotic microangiopathy as a cause of cardiovascular toxicity from the BCR-ABL1 tyrosine kinase inhibitor ponatinib. Blood, 133(14). https://doi.org/10.1182/blood-2018-10-881557

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[1] Plana, J. C., Galderisi, M., Barac, A., Ewer, M. S., Ky, B., Scherrer-Crosbie, M., et al. (2014). Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. European Heart Journal Cardiovascular Imaging, 15(10), 1063–1093. https://doi.org/10.1093/ehjci/jeu192 - DOI - PubMed - PMC

[2] Plana, J. C., Galderisi, M., Barac, A., Ewer, M. S., Ky, B., Scherrer-Crosbie, M., et al. (2014). Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. European Heart Journal Cardiovascular Imaging, 15(10), 1063–1093. https://doi.org/10.1093/ehjci/jeu192 - DOI - PubMed - PMC

[3] Curigliano, G., Cardinale, D., Suter, T., Plataniotis, G., De Azambuja, E., Sandri, M. T., et al. (2012). Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO clinical practice guidelines. Annals of Oncology, 23(SUPPL. 7). https://doi.org/10.1093/annonc/mds293

[4] Curigliano, G., Cardinale, D., Suter, T., Plataniotis, G., De Azambuja, E., Sandri, M. T., et al. (2012). Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO clinical practice guidelines. Annals of Oncology, 23(SUPPL. 7). https://doi.org/10.1093/annonc/mds293

[5] Li, D. L., Wang, Z. V., Ding, G., Tan, W., Luo, X., Criollo, A., et al. (2016). Doxorubicin blocks cardiomyocyte autophagic flux by inhibiting lysosome acidification. Circulation, 133(17), 1668–1687. https://doi.org/10.1161/CIRCULATIONAHA.115.017443 - DOI - PubMed - PMC

[6] Li, D. L., Wang, Z. V., Ding, G., Tan, W., Luo, X., Criollo, A., et al. (2016). Doxorubicin blocks cardiomyocyte autophagic flux by inhibiting lysosome acidification. Circulation, 133(17), 1668–1687. https://doi.org/10.1161/CIRCULATIONAHA.115.017443 - DOI - PubMed - PMC

[7] Asnani, A., Moslehi, J. J., Adhikari, B. B., Baik, A. H., Beyer, A. M., De Boer, R. A., et al. (2021). Preclinical models of cancer therapy-associated cardiovascular toxicity: A scientific statement from the American Heart Association. Circulation Research. https://doi.org/10.1161/RES.0000000000000473 - DOI - PubMed - PMC

[8] Asnani, A., Moslehi, J. J., Adhikari, B. B., Baik, A. H., Beyer, A. M., De Boer, R. A., et al. (2021). Preclinical models of cancer therapy-associated cardiovascular toxicity: A scientific statement from the American Heart Association. Circulation Research. https://doi.org/10.1161/RES.0000000000000473 - DOI - PubMed - PMC

[9] Latifi, Y., Moccetti, F., Wu, M., Xie, A., Packwood, W., Qi, Y., et al. (2019). Thrombotic microangiopathy as a cause of cardiovascular toxicity from the BCR-ABL1 tyrosine kinase inhibitor ponatinib. Blood, 133(14). https://doi.org/10.1182/blood-2018-10-881557

[10] Latifi, Y., Moccetti, F., Wu, M., Xie, A., Packwood, W., Qi, Y., et al. (2019). Thrombotic microangiopathy as a cause of cardiovascular toxicity from the BCR-ABL1 tyrosine kinase inhibitor ponatinib. Blood, 133(14). https://doi.org/10.1182/blood-2018-10-881557

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In Vivo Murine Models of Cardiotoxicity Due to Anticancer Drugs: Challenges and Opportunities for Clinical Translation

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In Vivo Murine Models of Cardiotoxicity Due to Anticancer Drugs: Challenges and Opportunities for Clinical Translation

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