Genetics of Anthracycline-Mediated Cardiotoxicity: Current Status and Challenges
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GENETICS (A.T. OWENS AND N. REZA, SECTION EDITORS)
Genetics of Anthracycline-Mediated Cardiotoxicity: Current Status and Challenges Chris McDermott-Roe 1,2 & Bonnie Ky 1,2,3,4,5 Published online: 8 August 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Purpose of Review Anthracyclines are potent and widely used anti-cancer compounds which carry a significant risk of cardiotoxicity. Genetic background is a key determinant of risk susceptibility and identifying causal genes and polymorphisms is an area of intense and growing interest. In this review, we provide an overview of the strategies employed to identify causal alleles and key findings stemming from recent studies. Recent Findings We describe candidate gene association studies and genome-wide association studies of anthracycline cardiotoxicity and summarize key findings. The importance of data robustness is discussed, as well as the largely untapped potential of stem cell–based strategies for both validation and discovery purposes. Summary Multi-disciplinary and coordinated efforts will be vital to fully understand the link between genetic background and anthracycline cardiotoxicity risk. Doing so will enhance understanding of pathological mechanisms and enable more personalized and nuanced treatment strategies for patients undergoing anthracycline chemotherapy. Keywords Anthracyclines . Cardiotoxicity . Cardio-oncology . Genetics
Introduction Anthracyclines are potent and broad-spectrum chemotherapeutic compounds used to treat various hematologic and solid This article is part of Topical Collection on Genetics * Chris McDermott-Roe [email protected] * Bonnie Ky [email protected] 1
Cardiovascular Institute, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
2
Smilow Center for Translational Research, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA
3
Division of Cardiology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
4
Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
5
Department of Biostatistics, Epidemiology & Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA 19104, USA
tumor malignancies in adults and in children, including leukemia, lymphoma, breast cancer, and sarcoma. Anthracyclinebased chemotherapy represents a cornerstone of the anticancer regimen and has led to marked survival gains [1]. Despite these successes, anthracyclines can elicit serious side effects and those impacting the cardiovascular system can be especially severe. Anthracycline-induced cardiotoxicity refers to the adverse effects on cardiac function and can range from an asymptomatic decline in ejection fraction to heart failure [2, 3]. Anthracycline cardiotoxicity is common, affecting an estimated 9–18% of patients. Symptom onset is variable, occurring an
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