Clinical Physiology of Circulation

ISSN 1814-6910 (Print)
ISSN 2410-9134 (Online)

 

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery


Issue's catalogue ➤ КФК. 2025; 22 (3): 199-286 ➤ Генетические основы кардиотоксичности: от механизмов к персонализированной медицине

Genetic aspects of cardiotoxicity: from mechanisms to personalized medicine

Authors: Buziashvili Yu.I., Matskeplishvili S.T., Asymbekova E.U., Tugeeva E.F., Akildzhonov F.R.

Company:
Bakoulev National Medical Research Center for Cardiovascular Surgery, Moscow, Russian Federation

E-mail: Сведения доступны для зарегистрированных пользователей.

DOI: https://doi.org/10.24022/1814-6910-2025-22-3-203-211

UDC: 616.12-009.3:612.314.2

Link: Clinical Physiology of Blood Circulaiton. 2025; 22 (3): 203-212

Quote as: Buziashvili Yu.I., Matskeplishvili S.T., Asymbekova E.U., Tugeeva E.F., Akildzhonov F.R. Genetic aspects of cardiotoxicity: from mechanisms to personalized medicine. Clinical Physiology of Circulation. 2025; 22 (3): 203–211 (in Russ.). DOI: 10.24022/1814-6910-2025-22-3-203-211

Keywords:  cardiotoxicity genetics cardiooncology

Received / Accepted:  04.08.2025 / 25.08.2025

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Abstract

The development of effective anticancer therapies over the past three decades has contributed to a decrease in cancer mortality. Despite existing clinical guidelines, identifying high-risk patients remains challenging. Genetic screening based on a patient’s genotype offers a more accurate method for assessing the risk of cardiotoxicity. Genetic variations can help identify patients with an increased likelihood of developing cardiotoxicity, opening up new opportunities to understand its mechanisms and develop personalized approaches to treatment and prevention. However, further research aimed at refining genetic markers, developing risk stratification algorithms, and improving patient monitoring methods is needed to implement such methods in clinical practice.

References

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****
  1. Buziashvili Yu.I., Stilidi I.S., Mackeplishvili S.T., Asymbekova E.U., Tugeeva E.F., Artamonova E.V. et al. Cardiovascular and oncological diseases – focus on modifiable risk factors and modern pathogenetic aspects. Annals of the Russian academy of medical sciences. 2023; 78(2): 132–140 (in Russ.). DOI: 10.15690/vramn8359
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  9. Chang V.Y., Wang J.J. Pharmacogenetics of chemotherapy-induced cardiotoxicity. Curr. Oncol. Rep. 2018; 20 (7): 52. DOI: 10.1007/s11912- 018-0696-8
  10. Wallace K.B., Sardão V.A., Oliveira P.J. Mitochondrial determinants of DOXORUBICIN-INDUCED Cardiomyopathy. Circ. Res. 2020; 126(7): 926–941. DOI: 10.1161/CIRCRESAHA.119.314681
  11. Pecoraro M., Pinto A., Popolo A. Trastuzumab-induced cardiotoxicity and role of mitochondrial connexin43 in the adaptive response. Toxicol. In. Vitro. 2020; 67: 104926. DOI: 10.1016/j.tiv.2020.104926
  12. Zhang J.J., Du J., Kong N., Zhang G.Y., Liu M.Z., Liu C. Mechanisms and pharmacological applications of ferroptosis: a narrative review. Ann. Transl. Med. 2021; 9 (19): 1503. DOI: 10.21037/atm-21-1595
  13. Tocchetti C.G., Farmakis D., Koop Y., Andres M.S., Couch L.S., Formisano L. et al. Cardiovascular toxicities of immune therapies for cancer – a scientific statement of the Heart Failure Association (HFA) of the ESC and the ESC Council of Cardio-Oncology. Eur. J. Heart Fail. 2024; 26 (10): 2055–2076. DOI: 10.1002/ejhf.3340
  14. Tripaydonis A., Conyers R., Elliott D.A. Pediatric anthracycline-induced cardiotoxicity: mechanisms, pharmacogenomics, and pluripotent stem-cell modeling. Clin. Pharmacol. Ther. 2019; 105 (3): 614–624. DOI: 10.1002/cpt.1311
  15. Ding Y., Du K., Niu Y.J., Wang Y., Xu X. Genetic susceptibility and mechanisms underlying the pathogenesis of anthracycline-associated cardiotoxicity. Oxid. Med. Cell. Longev. 2022; 2022: 5818612. DOI: 10.1155/2022/5818612
  16. Park B., Sim S.H., Lee K.S., Kim H.J., Park I.H. Genome-wide association study of genetic variants related to anthracycline-induced cardiotoxicity in early breast cancer. Cancer. Sci. 2020; 111 (7): 2579–2587. DOI: 10.1111/cas.14446
  17. Sayed N., Ameen M., Wu J.C. Personalized medicine in cardio-oncology: the role of induced pluripotent stem cell. Cardiovasc. Res. 2019; 115 (5): 949–959. DOI: 10.1093/cvr/cvz024
  18. Antoniadi K., Thomaidis N., Nihoyannopoulos P., Toutouzas K., Gikas E., Kelaidi C. et al. Prognostic factors for cardiotoxicity among children with cancer: definition, causes, and diagnosis with omics technologies. Diagnostics (Basel). 2023; 13 (11): 1864. DOI: 10.3390/ diagnostics13111864
  19. Magdy T., Jouni M., Kuo H.H., Weddle C.J., Lyra-Leite D., Fonoudi H. et al. Identification of drug transport er genomic variants and inhibitors that protect against doxorubicin-induced cardiotoxicity. Circulation. 2022; 145 (4): 279–294. DOI: 10.1161/CIRCULATIONAHA.121.055801
  20. Visscher H., Rassekh S.R., Sandor G.S., Caron H.N., van Dalen E.C., Kremer L.C. et al. Genetic variants in SLC22A17 and SLC22A7 are associated with anthracycline-induced cardiotoxicity in children. Pharmacogenomics. 2015; 16 (10): 1065–1076. DOI: 10.2217/pgs.15.61
  21. Tran D.H., Wang Z.V. Glucose metabolism in cardiac hypertrophy and heart failure. J. Am. Heart Assoc. 2019; 8 (12): e012673. DOI: 10.1161/JAHA.119.012673
  22. Yuan Y., Fan S., Shu L., Huang W., Xie L., Bi C. et al. Exploration the mechanism of doxorubicin-induced heart failure in rats by integration of proteomics and metabolomics data. Front. Pharmacol. 2020; 11: 600561. DOI: 10.3389/fphar.2020.600561
  23. Siemens A., Rassekh S.R., Ross C.J., Carleton B. Development of a dose-adjusted polygenic risk model for anthracycline-induced cardiotoxicity. Ther. Drug. Monit. 2023; 45 (3): 337–344. DOI: 10.1097/FTD.0000000000001077
  24. Singh P., Wang X., Hageman L., Chen Y., Magdy T., Landier W. et al. Association of GSTM1 null variant with anthracycline-related cardiomyopathy after childhood cancer-A Children’s Oncology Group ALTE03N1 report. Cancer. 2020; 126 (17): 4051–4058. DOI: 10.1002/ cncr.32948
  25. Wang X., Singh P., Zhou L., Sharafeldin N., Landier W., Hageman L. et al. Genome-wide association study identifies ROBO2 as a novel susceptibility gene for anthracycline-related cardiomyopathy in childhood cancer survivors. J. Clin. Oncol. 2023; 41 (9): 1758–1769. DOI: 10.1200/JCO.22.01527
  26. Wang Y.Z., Cao M.L., Liu Y.W., He Y.Q., Yang C.X., Gao F. CD44 mediates oligosaccharides of hyaluronan-induced proliferation, tube formation and signal transduction in endothelial cells. Exp. Biol. Med. (Maywood). 2011; 236 (1): 84–90. DOI: 10.1258/ebm.2010.010206
  27. Sapkota Y., Ehrhardt M.J., Qin N., Wang Z., Liu Q., Qiu W. et al. A novel locus on 6p21.2 for cancer treatment-induced cardiac dysfunction among childhood cancer survivors. J. Natl. Cancer. Inst. 2022; 114 (8): 1109–1116. DOI: 10.1093/jnci/djac115
  28. Lang J.K., Karthikeyan B., Quiñones-Lombraña A., Blair R.H., Early A.P., Levine E. et al. CBR3 V244M is associated with LVEF reduction in breast cancer patients treated with doxorubicin. Cardiooncology. 2021; 7 (1): 17. DOI: 10.1186/s40959-021-00103-0
  29. Advani P.P., Ruddy K.J., Herrmann J., Ray J.C., Craver E.C., Yothers G. et al. Replication of genetic associations of chemotherapy-related cardiotoxicity in the adjuvant NSABP B-31 clinical trial. Front. Oncol. 2023; 13: 1139347. DOI: 10.3389/fonc.2023.1139347
  30. Serie D.J., Crook J.E., Necela B.M., Dockter T.J., Wang X., Asmann Y. et al. Genome-wide association study of cardiotoxicity in the NCCTG N9831 (Alliance) adjuvant trastuzumab trial. Pharmacogenet. Genomics. 2017; 27 (10): 378–385. DOI: 10.1097/FPC.0000000000000302
  31. Aminkeng F., Bhavsar A.P., Visscher H., Rassekh S.R., Li Y., Lee J. et al. A coding variant in RARG confers susceptibility to anthracycline- induced cardiotoxicity in childhood cancer. Nat. Genet. 2015; 47 (9): 1079–1084. DOI: 10.1038/ng.3374
  32. Garcia-Pavia P., Kim Y., Restrepo-Cordoba M.A., Lunde I.G., Wakimoto H., Smith A.M. et al. Genetic variants associated with cancer therapy-induced cardiomyopathy. Circulation. 2019; 140 (1): 31–41. DOI: 10.1161/CIRCULATIONAHA.118.037934
  33. Giza D.E., Iliescu G., Hassan S., Marmagkiolis K., Iliescu C. Cancer as a risk factor for cardiovascular disease. Curr. Oncol. Rep. 2017; 19(6): 39. DOI: 10.1007/s11912-017-0601-x
  34. Tan A., Im S.A., Mattar A., Colomer R., Stroyakovskii D., Nowecki Z. et al. Fixed-dose combination of pertuzumab and trastuzumab for subcutaneous injection plus chemotherapy in HER2-positive early breast cancer (FeDeriCa): a randomised, open-label, multicentre, non- inferiority, phase 3 study. Lancet Oncol. 2021; 22 (1): 85–97. DOI: 10.1016/S1470-2045(20)30536-2
  35. Swain S., Miles D., Kim S., Im Y.H., Im S.A., Semiglazov V. et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020; 21 (4): 519–530. DOI: 10.1016/S1470-2045(19)30863-0
  36. Udagawa C., Kuah S., Shimoi T., Kato K., Yoshida T., Nakano M. et al. Replication Study for the Association of Five SNPs Identified by GWAS and Trastuzumab-Induced Cardiotoxicity in Japanese and Singaporean Cohorts. Biol. Pharm. Bull. 2022; 45 (8): 1198–1202. DOI: 10.1248/bpb.b22-00136
  37. Udagawa C., Nakamura H., Ohnishi H., Tamura K., Shimoi T., Yoshida M. et al. Whole exome sequencing to identify genetic markers for trastuzumab-induced cardiotoxicity. Cancer Sci. 2018; 109 (2): 446–452. DOI: 10.1111/cas.13471
  38. Perdigoto A.L., Kluger H., Herold K.C. Adverse events induced by immune checkpoint inhibitors. Curr. Opin. Immunol. 2021; 69: 29–38. DOI: 10.1016/j.coi.2021.02.002
  39. Qu S., Zhang J., Wang K., Zhou Y. Identification of key immune-related genes and potential therapeutic targets in immune checkpoint inhibitor-associated myocarditis. Postgrad. Med. J. 2025; 101 (1192): 137–146. DOI: 10.1093/postmj/qgae117
  40. Ren J., Jiang L., Liu X., Liao Y., Zhao X., Tang F. et al. Heart-specific DNA methylation analysis in plasma for the investigation of myocardial damage. J. Transl. Med. 2022; 20 (1): 36. DOI: 10.1186/s12967-022-03234-9
  41. Shah S. Genomics for improving heart failure risk assessment in cancer patients. JACC CardioOncol. 2024; 6 (5): 728–730. DOI: 10.1016/j.jaccao.2024.06.001

About Authors

  • Yurij I. Buziashvili, Dr. Med. Sci., Professor, Academician of the Russian Academy of Sciences, Head of the Clinico-Diagnostic Department; ORCID
  • Simon T. Mackeplishvili, Dr. Med. Sci., Professor, Corresponding Member of Russian Academy of Science, Chief Researcher; ORCID
  • Elmira U. Asymbekova, Dr. Med. Sci., Leading Researcher; ORCID
  • Elvina F. Tugeeva, Dr. Med. Sci., Leading Researcher; ORCID
  • Firdavsdzhon R. Akildzhonov, Cand. Med. Sci., Junior Researcher; ORCID

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