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Cardioprotective Strategies for Doxorubicin-induced Cardiotoxicity: Present and Future

https://doi.org/10.20996/1819-6446-2022-02-11

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Abstract

The improvement of drugs and protocols of chemotherapeutic treatment has led to improved outcomes and survival in patients with cancer. But along with this, at first glance a positive point, there was another interdisciplinary problem, which is the need for early detection and treatment of developing cardiotoxicity when taking chemotherapy drugs. The study of cardioprotective strategies has recently become increasingly relevant, due to the fact that many patients who have successfully undergone treatment for cancer have a high risk of developing or are at high risk of death from cardiovascular diseases. One of the main drugs for the treatment of a number of oncological diseases is an anthracycline – type antibiotic-doxorubicin. This review briefly examines the risk factors and pathophysiological mechanisms underlying anthracycline cardiotoxicity. The current possibilities of cardioprotection of anthracycline cardiotoxicity are considered in detail, and some promising targets and drugs for improving cardioprotective strategies are discussed.

About the Authors

A. M. Chaulin
Samara State Medical University; Samara Regional Cardiology Dispensary
Russian Federation

Aleksey M. Chaulin.

Samara.

eLibrary SPIN 1107-0875



D. V. Duplyakov
Samara State Medical University; Samara Regional Cardiology Dispensary
Russian Federation

Dmitry V. Duplyakov.

Samara.

eLibrary SPIN 5665-9578



References

1. Meijers WC, de Boer RA. Common risk factors for heart failure and cancer. Cardiovasc Res. 2019;115(5):844-853. DOI:10.1093/cvr/cvz035.

2. Ferlay J, Colombet M, Soerjomataram I, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 2018;103:356-87. DOI:10.1016/j.ejca.2012.12.027.

3. Chaulin AM, Karslyan LS, Bazyuk EV, et al. Clinical and Diagnostic Value of Cardiac Markers in Human Biological Fluids. Kardiologiia. 2019;59(11):66-75 (In Russ) DOI:10.18087/cardio.2019.11.n414.

4. Bluethmann SM, Mariotto AB, Rowland JH. Anticipating the "silver tsunami": prevalence trajectories and comorbidity burden among older Cancer survivors in the United States. Cancer Epidemiol Biomark Prev. 2016;25(7):1029-36. DOI:10.1158/1055-9965.EPI-16-0133.

5. Armenian SH, Xu L, Ky B, et al. Cardiovascular disease among survivors of adult-onset cancer: a community-based retrospective cohort study. J Clin Oncol. 2016;34(10):1122-30. DOI:10.1200/JCO.2015.64.0409.

6. Chaulin AM, Abashina OE, Duplyakov DV. Pathophysiological mechanisms of cardiotoxicity in chemotherapeutic agents. Russian Open Medical Journal. 2020;9:e0305. DOI:10.15275/rusomj.2020.0305.

7. Gendlin GE, Emelina EI, Nikitin IG, Vasyuk YuA. Modern view on cardiotoxicity of chemotherapeutics in oncology including anthracyclines. Russian Journal of Cardiology. 2017;(3):145-54 (In Russ.) DOI:10.15829/1560-4071-2017-3-145-154.

8. Cardinale D, Colombo A, Lamantia G, et al. Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy. J Am Coll Cardiol. 2010;55(3):213-20. DOI:10.1016/j.jacc.2009.03.095.

9. Lyon AR, Dent S, Stanway S, et al. Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a position statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society. Eur J Heart Fail. 2020;22(11):1945-60. DOI:10.1002/ejhf.1920.

10. Vasyuk YA, Shupenina EY, Novosel EO, Agapov IS. Heart rhythm and conduction disorders as manifestations of cardiotoxicity of anticancer treatment: myth or reality? Siberian Medical Journal. 2020;35(1):13-21 (In Russ.) DOI:10.29001/2073-8552-2020-35-1-13-21.

11. Chaulin AM, Duplyakov DV. Arrhythmogenic effects of doxorubicin. Complex Issues of Cardiovascular Diseases. 2020;9(3):69-80 (In Russ.) DOI:10.17802/2306-1278-2020-9-3-69-80.

12. Zamorano JL, Lancellotti P, Rodriguez Munoz D, et al. 2016 ESC position paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: the task force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J. 2016;37(36):2768-801. DOI:10.1093/eurheartj/ehw211.

13. Armenian SH, Lacchetti C, Barac A, et al. Prevention and Monitoring of Cardiac Dysfunction in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2017;35(8):893-911. DOI:10.1200/JCO.2016.70.5400.

14. Lancellotti P, Suter TM, López-Fernández T, et al. Cardio-Oncology Services: rationale, organization, and implementation. Eur Heart J. 2019;40(22):1756-63. DOI:10.1093/eurheartj/ehy453.

15. Tilemann LM, Heckmann MB, Katus HA, et al. Cardio-oncology: conflicting priorities of anticancer treatment and cardiovascular outcome. Clin Res Cardiol. 2018;107(4):271-80. DOI:10.1007/s00392-018-1202-x.

16. Vasyuk YuA, Nesvetov VV, Shkolnik EL, et al. Possibilities of modern echocardiographic technologies in the early diagnosis of the cardiotoxic effect of chemotherapy drugs anthracycline series in cancer patients. Kardiologiia. 2017;57(4S):31-7 (In Russ.) DOI:10.18087/cardio.2417.

17. Runowicz CD, Leach CR, Henry NL, et al. American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline. J Clin Oncol. 2016;34(6):611-35. DOI:10.1200/JCO.2015.64.3809.

18. Chaulin AM, Duplyakov DV. Increased natriuretic peptides, not associated with heart failure. Russian Journal of Cardiology. 2020;25(4S):4140 (In Russ.) DOI:10.15829/1560-4071-2020-4140.

19. Chaulin AM, Abashina OE, Duplyakov DV. High-sensitivity cardiac troponins: detection and central analytical characteristics. Cardiovascular Therapy and Prevention. 2021;20(2):2590 (In Russ.) DOI:10.15829/1728-8800-2021-2590.

20. Sarzhevskii VO, Kolesnikova DS, Mel’nichenko VYa. Biochemical markers of cardiotoxicity of high-dose chemotherapy and autologous hematopoietic stem cell transplantation in patients with malignant lymphoproliferative disorders. Clinical Oncohematology. 2016;9(4):465-73 (In Russ.) DOI:10.21320/2500-2139-2016-9-4-465-473.

21. Jones M, O'Gorman P, Kelly C, et al. High-sensitive cardiac troponin-I facilitates timely detection of subclinical anthracycline-mediated cardiac injury. Ann Clin Biochem. 2017;54(1):149-57. DOI:10.1177/0004563216650464.

22. Sawaya H, Sebag IA, Plana JC, et al. Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imaging. 2012;5(5):596–603. DOI:10.1161/CIRCIMAGING.112.973321.

23. Jensen BT, Lien CY, Hydock DS, et al. Exercise mitigates cardiac doxorubicin accumulation and preserves function in the rat. J Cardiovasc Pharmacol. 2013;62(3):263-9. DOI:10.1097/FJC.0b013e3182982ce0.

24. Irwin ML, Crumley D, McTiernan A, et al. Physical activity levels before and after a diagnosis of breast carcinoma: the health, eating, activity, and lifestyle (HEAL) study. Cancer. 2003;97(7):1746-57. DOI:10.1002/cncr.11227.

25. Rock CL, Flatt SW, Newman V, et al. Factors associated with weight gain in women after diagnosis of breast cancer. Women's healthy eating and living study group. J Am Diet Assoc. 1999;99(10):1212-21. DOI:10.1016/s0002-8223(99)00298-9.

26. Ashraf J, Roshan VD. Is short-term exercise a therapeutic tool for improvement of cardioprotection against DOX-induced cardiotoxicity? An experimental controlled protocol in rats. Asian Pac J Cancer Prev. 2012;13(8):4025-30. PMID: 23098511.

27. Aakre KM, Omland T. Physical activity, exercise and cardiac troponins: Clinical implications. Prog Cardiovasc Dis. 2019;62(2):108-115. DOI:10.1016/j.pcad.2019.02.005.

28. Schmitz KH, Courneya KS, Matthews C, et al. American College of Sports Medicine roundtable on exercise guidelines for cancer survivors. Med Sci Sports Exerc. 2010;42(7):1409-26. DOI:10.1249/MSS.0b013e3181e0c112.

29. van Dalen EC, van der Pal HJ, Kremer LC. Different dosage schedules for reducing cardiotoxicity in people with cancer receiving anthracycline chemotherapy. Cochrane Database Syst Rev. 2016;3(3):CD005008. DOI:10.1002/14651858.CD005008.pub4.

30. Sercombe L, Veerati T, Moheimani F, et al. Advances and challenges of liposome assisted drug delivery. Front Pharmacol. 2015;6:286. DOI:10.3389/fphar.2015.00286.

31. Rukavitsin OA, Pop VP. Pegylated liposomal doxorubicin (caelyx) in oncohematology: modern aspects. Oncohematology. 2008;(1-2):75-84 (In Russ.)

32. Artamonova EV. Place of pegylated liposomal doxorubicin in the therapy of metastatic breast cancer. Tumors of Female Reproductive System. 2016;12(2):35-45 (In Russ.) DOI:10.17650/1994-4098-2016-12-2-35-45.

33. Schloemer NJ, Brickler M, Hoffmann R, et al. Administration of dexrazoxane improves cardiac indices in children and young adults with acute myeloid leukemia (AML) while maintaining survival out-comes. J Pediatr Hematol Oncol. 2017;39(5):e254-e8. DOI:10.1097/MPH.0000000000000838.

34. Reichardt P, Tabone MD, Mora J, et al. Risk-benefit of dexrazoxane for preventing anthracy-cline-related cardiotoxicity: re-evaluating the European labeling. Future Oncol. 2018;14(25):2663-76. DOI:10.2217/fon-2018-0210.

35. Zhou L, Sung RY, Li K, et al. Cardioprotective effect of dexrazoxane in a rat model of myocardial infarction: anti-apoptosis and promoting angiogenesis. Int J Cardiol. 2011;152(2):196-201. DOI:10.1016/j.ijcard.2010.07.015.

36. Xiang P, Deng HY, Li K, et al. Dexrazoxane protects against doxorubicin-induced cardiomyopathy: upregulation of Akt and Erk phosphorylation in a rat model. Cancer Chemother Pharmacol. 2009;63(2):343-49. DOI:10.1007/s00280-008-0744-4.

37. Oesterle A, Laufs U, Liao JK. Pleiotropic effects of statins on the cardiovascular system. Circ Res. 2017;120(1):229-43. DOI:10.1161/CIRCRESAHA.116.308537.

38. Seicean S, Seicean A, Plana JC, et al. Effect of statin therapy on the risk for incident heart failure in patients with breast cancer receiving anthracycline chemotherapy: an observational clinical cohort study. J Am Coll Cardiol. 2012;60(23):2384-90. DOI:10.1016/j.jacc.2012.07.067.

39. Chotenimitkhun R, D'Agostino RJr, Lawrence JA, et al. Chronic statin administration may attenuate early anthracycline associated declines in left ventricular ejection function. Can J Cardiol. 2015;31(3):302-7. DOI:10.1016/j.cjca.2014.11.020.

40. Mendieta G, Ben-Aicha S, Casani L, et al. Molecular pathways involved in the cardioprotective effects of intravenous statin administration during ischemia. Basic Res Cardiol. 2019;115(1):2. DOI:10.1007/s00395-019-0760-z.

41. Zhang L, Cheng L, Wang Q, et al. Atorvastatin protects cardiomyocytes from oxidative stress by inhibiting LOX-1 expression and cardiomyocyte apoptosis. Acta Biochim Biophys Sin (Shang-hai). 2015;47(3):174-82. DOI:10.1093/abbs/gmu131.

42. Riad A, Bien S, Westermann D, et al. Pretreatment with statin attenuates the cardiotoxicity of Doxorubicin in mice. Cancer Res. 2009;69(2):695-9. DOI:10.1158/0008-5472.CAN-08-3076.

43. Lankin VZ, Tikhaze AK, Konovalova GG. The influence of hypolipidemic therapy on the level of modified low density lipoproteides. Russian Journal of Cardiology. 2018;(8):39-44 (In Russ.) DOI:10.15829/1560-4071-2018-8-39-44.

44. Unlu S, Nurkoç SG, Sezenoz B, et al. Impact of statin use on high sensitive troponin T levels with moderate exercise. Acta Cardiol. 2019;74(5):380-5. DOI:10.1080/00015385.2018.1510801.

45. Godoy JC, Niesman IR, Busija AR, et al. Atorvastatin, but not pravastatin, inhibits cardiac Akt/mTOR signaling and disturbs mitochondrial ultrastructure in cardiac myocytes. FASEB J. 2019;33(1):1209-25. DOI:10.1096/fj.201800876R.

46. Nabati M, Janbabai G, Baghyari S, et al. Cardioprotective effects of Carvedilol in inhibiting doxorubicin-induced cardiotoxicity. J Cardiovasc Pharmacol. 2017;69(5):279-85. DOI:10.1097/FJC.0000000000000470.

47. Avila MS, Ayub-Ferreira SM, de Barros Wanderley MRJr, et al. Carvedilol for Prevention of Chemotherapy-Related Cardiotoxicity: The CECCY Trial. J Am Coll Cardiol. 2018;71(20):2281-90. DOI:10.1016/j.jacc.2018.02.049.

48. Kaya MG, Ozkan M, Gunebakmaz O, et al. Protective effects of nebivolol against anthracycline-induced cardiomyopathy: a randomized control study. Int J Cardiol. 2013;167(5):2306-10. DOI:10.1016/j.ijcard.2012.06.023.

49. Gulati G, Heck SL, Ree AH, et al. Prevention of cardiac dysfunction during adjuvant breast cancer therapy (PRADA): a 2 x 2 factorial, randomized, placebo-controlled, double-blind clinical trial of candesartan and metoprolol. Eur Heart J. 2016;37(21):1671-80. DOI:10.1093/eurheartj/ehw022.

50. Liu J, Masoudi FA, Spertus JA, et al. Patterns of use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers among patients with acute myocardial infarction in China from 2001 to 2011: China PEACE-Retrospective AMI Study. J Am Heart Assoc. 2015;4(2):e001343. DOI:10.1161/JAHA.114.001343.

51. Cardinale D, Colombo A, Sandri MT, et al. Prevention of high-dose chemotherapy-induced cardiotoxicity in high-risk patients by angiotensin-converting enzyme inhibition. Circulation. 2006;114(23):2474-81. DOI:10.1161/CIRCULATIONAHA.106.635144.

52. Chan KY, Zhou L, Xiang P, et al. Thrombopoietin improved ventricular function and regulated remodeling genes in a rat model of myocardial infarction. Int J Cardiol. 2013;167(6):2546-54. DOI:10.1016/j.ijcard.2012.06.038.

53. Li R, Huang Y, Semple I, et al. Cardioprotective roles of sestrin 1 and sestrin 2 against doxorubicin cardiotoxicity. Am J Physiol Heart Circ Physiol. 2019;317(1):H39-H48. DOI:10.1152/ajp-heart.00008.2019.

54. Wang X, Wang XL, Chen HL. et al. Ghrelin inhibits doxorubicin cardiotoxicity by inhibiting excessive autophagy through AMPK and p38-MAPK. Biochem Pharmacol. 2014;88(3):334-50. DOI:10.1016/j.bcp.2014.01.040.

55. Kida Y, Goligorsky MS. Sirtuins, Cell Senescence, and Vascular Aging. Can J Cardiol. 2016;32(5):634-41. DOI:10.1016/j.cjca.2015.11.022.

56. Ruan Y, Dong C, Patel J, et al. SIRT1 suppresses doxorubicin-induced cardiotoxicity by regulating the oxidative stress and p38MAPK pathways. Cell Physiol Biochem. 2015;35(3):1116-24. DOI:10.1159/000373937.

57. Gu J, Hu W, Zhang DD. Resveratrol, a polyphenol phytoalexin, protects against doxorubicin-induced cardiotoxicity. J Cell Mol Med. 2015;19(10):2324-8. DOI:10.1111/jcmm.12633.

58. Lou Y, Wang Z, Xu Y, et al. Resveratrol prevents doxorubicin-induced cardiotoxicity in H9c2 cells through the inhibition of endoplasmic reticulum stress and the activation of the Sirt1 pathway. Int J Mol Med. 2015;36(3):873-80. DOI:10.3892/ijmm.2015.2291.

59. Zhang C, Feng Y, Qu S, et al. Resveratrol attenuates doxorubicin-induced cardiomyocyte apoptosis in mice through SIRT1-mediated deacetylation of p53. Cardiovasc Res. 2011;90(3):538-45. DOI:10.1093/cvr/cvr022.


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Chaulin A.M., Duplyakov D.V. Cardioprotective Strategies for Doxorubicin-induced Cardiotoxicity: Present and Future. Rational Pharmacotherapy in Cardiology. 2022;18(1):103-112. (In Russ.) https://doi.org/10.20996/1819-6446-2022-02-11

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ISSN 1819-6446 (Print)
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