ABSTRACT:
Nowadays, cancer and cardiovascular diseases rank among the world's major causes of death. It is predicted that around 26 million cancer survivors will be at a risk of developing cardiovascular complications by 2040. In an effort to lessen the cardiotoxic effects of cancer treatments, the area of cardio-oncology was founded in the early to mid-2000s. Doxorubicin (DOX), an anthracycline-based anticancer medication, has limited efficacy in cancer patients due to its cardiotoxic effects. The primary objective of this literature review is to help with the early detection and treatment of cardiac problems by understanding the involvement of several biomarkers in doxorubicin-induced cardiotoxicity (DIC). MicroRNAs (miRNAs) are stable and detectable in body fluids, and exosomes (EXOs), present in various cell components, show promising ability as a biomarker in DIC. However, further research is needed to develop their potential as biomarkers and to improve patient outcomes in cardio-oncology.
Cite this article:
Akshaya Iyer, Mateen Sayyed. Biomarkers for Early Detection of Doxorubicin-Induced Cardiotoxicity: A Focus on miRNAs and EXOs. Research Journal of Pharmacy and Technology. 2025;18(9):4548-4. doi: 10.52711/0974-360X.2025.00653
Cite(Electronic):
Akshaya Iyer, Mateen Sayyed. Biomarkers for Early Detection of Doxorubicin-Induced Cardiotoxicity: A Focus on miRNAs and EXOs. Research Journal of Pharmacy and Technology. 2025;18(9):4548-4. doi: 10.52711/0974-360X.2025.00653 Available on: https://rjptonline.org/AbstractView.aspx?PID=2025-18-9-73
REFERENCES:
1. ReFaey K, Tripathi S, Grewal SS, Bhargav AG, Quinones DJ, Chaichana KL, et al. Cancer Mortality Rates Increasing vs Cardiovascular Disease Mortality Decreasing in the World: Future Implications. Mayo Clin Proc Innov Qual Outcomes. 2021; 5(3): 645-53.
2. Sparano JA, Sahni G. The ESC Cardio-Oncology Guidelines: A Roadmap for Clinical Practice and Generating Needed Evidence. JACC CardioOncol. 2023; 5(1): 141-4.
3. Witteles RM, Reddy SA. ESC Cardio-Oncology Guidelines: A Triumph-But Are We Overscreening? JACC Cardio Oncol. 2022; 5(1): 133-136.
4. Li G, Zhang L, Liu M. Evolving field of cardio-oncology. Cancer Pathogenesis and Therapy. 2023; 1(2): 141-5.
5. Lyon AR, López-Fernández T, Couch LS, Asteggiano R, Aznar MC, Bergler-Klein J, et al. 2022 ESC Guidelines on cardio-oncology developed in collaboration with the European Hematology Association (EHA), the European Society for Therapeutic Radiology and Oncology (ESTRO) and the International Cardio-Oncology Society (IC-OS). Eur Heart J. 2022; 43(41): 4229-4361.
6. Boulaares Islam, Derouiche Samir, Guemari Imane Yousra. Protective effect of ObE against Doxorubicin-Induced immunosuppression and Cardiotoxicity in Rats. Research Journal of Pharmacy and Technology. 2024; 17(4): 1839-3.
7. Zamorano JL, Lancellotti P, Rodriguez Muñoz D, Aboyans V, Asteggiano R, Galderisi M, 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): 2768-2801.
8. VKK Mandlem, N. Gouri Priya, M. Raghavendra, K. Abbulu. Evaluation of Cardioprotective Activity of Tamarindus indica Linn Pericarpic extract in Doxorubicin induced Cardiotoxicity in Experimental Rats. Research J. Pharm. and Tech. 2020; 13(7): 3267-3273.
9. Rawat PS, Jaiswal A, Khurana A, Bhatti JS, Navik U. Doxorubicin-induced cardiotoxicity: An update on the molecular mechanism and novel therapeutic strategies for effective management. Biomed Pharmacother. 2021; 139: 111708.
10. Rohan Pal, Rajat Subhra Saha, Sudipta Dey, Sumana Das. A Review on the Role of some Cardioprotective Natural Resources in Mitigating Doxorubicin-Induced Cardiotoxicity. Research Journal of Pharmacy and Technology. 2024; 17(6): 2933-2.
11. Nebigil CG, Désaubry L. Updates in Anthracycline-Mediated Cardiotoxicity. Front Pharmacol. 2018; Nov 12; 9: 1262.
12. Aithamraju Satish Chandra, P. Shanmugapandiyan. Cardioprotective efficacy of Tridax procumbens methanolic extract in Doxorubicin induced Oxidative Cardiac Damage. Research J. Pharm. and Tech. 2020; 13(1): 110-113.
13. P. Aruna, N. M. Gayathiri. Cardioprotective Activity of Telmisartan, Metformin and its Combination against Doxorubicin Induced Myocardial Infarction in Rat Model. Research J. Pharm. and Tech 2018; 11(12): 5293-5296.
14. Divya B, Shivashree S, K. Mruthunjaya, S. N. Manjula. Cardioprotective activity of Lawsonia inermis roots against Doxorubicin Treated Mice. Research J. Pharm. and Tech. 2020; 13(7): 3279-3283.
15. Wang T, Xing G, Fu T, Ma Y, Wang Q, Zhang S, et al. Role of mitochondria in doxorubicin-mediated cardiotoxicity: From molecular mechanisms to therapeutic strategies. Cell Stress Chaperones. 2024; 29(2): 349-357.
16. Fa HG, Chang WG, Zhang XJ, Xiao DD, Wang JX. Noncoding RNAs in doxorubicin-induced cardiotoxicity and their potential as biomarkers and therapeutic targets. Acta Pharmacol Sin. 2021; 42(4): 499-507.
17. Bodaghi A, Fattahi N, Ramazani A. Biomarkers: Promising and valuable tools towards diagnosis, prognosis and treatment of Covid-19 and other diseases. Heliyon. 2023; Feb;9(2):e13323.
18. Pradeep Sahu, Neha Pinkalwar, Ravindra Dhar Dubey, Shweta Paroha, Shilpi Chatterjee, Tanushree Chatterjee. Biomarkers: An Emerging Tool for Diagnosis of a Disease and Drug Development. Asian J. Res. Pharm. Sci. 2011; 1(1): 09-16
19. Ahmad A, Imran M, Ahsan H. Biomarkers as Biomedical Bioindicators: Approaches and Techniques for the Detection, Analysis, and Validation of Novel Biomarkers of Diseases. Pharmaceutics. 2023; 15(6): 1630.
20. Thupakula S, Nimmala SSR, Ravula H, Chekuri S, Padiya R. Emerging biomarkers for the detection of cardiovascular diseases. Egypt Heart J. 2022; 74(1): 77.
21. Chen L, Xu Y. MicroRNAs as Biomarkers and Therapeutic Targets in Doxorubicin-Induced Cardiomyopathy: A Review. Front Cardiovasc Med. 2021; 24; 8: 740515.
22. Zhang X, Sun Y, Zhang Y, Fang F, Liu J, Xia Y, et al. Cardiac Biomarkers for the Detection and Management of Cancer Therapy-Related Cardiovascular Toxicity. J Cardiovasc Dev Dis. 2022; 9(11): 372.
23. Kayani M, Fatima N, Yarra PC, Almansouri NE, K D, Balasubramanian A, et al. Novel Biomarkers in Early Detection of Heart Failure: A Narrative Review. Cureus. 2024; 16(2): 53445.
24. Sahil Mahajan, Heemani Dave, Santosh Bothe, Debarshikar Mahpatra, Sandeep Sonawane, Sanjay Kshirsagar, et al. Objective Monitoring of Cardiovascular Biomarkers using Artificial Intelligence (AI). Asian Journal of Pharmaceutical Research. 2022; 12(3): 229-4.
25. V. Jayashree, Malarkodi Velraj. Breast Cancer and various Prognostic Biomarkers for the diagnosis of the disease: A Review. Research J. Pharm. and Tech. 2017; 10(9): 3211-3216.
26. Song Z, Gao R, Yan B. Potential roles of microRNA-1 and microRNA-133 in cardiovascular disease. Rev Cardiovasc Med. 2020; 21(1): 57-64.
27. Liu MN, Luo G, Gao WJ, Yang SJ, Zhou H. miR-29 family: A potential therapeutic target for cardiovascular disease. Pharmacol Res. 2021; 166: 105510.
28. Xin Y, Yang C, Han Z. Circulating miR-499 as a potential biomarker for acute myocardial infarction. Ann Transl Med. 2016; 4(7): 135.
29. Zhang G, Yang X, Su X, An N, Yang F, Li X, et al. Understanding the Protective Role of Exosomes in Doxorubicin-Induced Cardiotoxicity. Oxid Med Cell Longev. 2022; 12; 2022:2852251.
30. Cheng L, Hill AF. Therapeutically harnessing extracellular vesicles. Nat Rev Drug Discov. 2022; 21(5): 379-399.
31. Yasir S J. Alrubaye, Mohammed B. Mohammed, Haidar A. Abdulamir. Exosome and Breast Cancer. Research Journal of Pharmacy and Technology. 2022; 15(3):1393-7.
32. Kalluri R, LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020; 7; 367(6478): 6977.
33. Yang B, Chen Y, Shi J. Exosome Biochemistry and Advanced Nanotechnology for Next-Generation Theranostic Platforms. Adv Mater. 2019; 31(2): 1802896.
34. Jiang L, Gu Y, Du Y, Liu J. Exosomes: Diagnostic Biomarkers and Therapeutic Delivery Vehicles for Cancer. Mol Pharm. 2019; 5; 16(8): 3333-3349.
35. Wani TU, Mohi-Ud-Din R, Mir RH, Itoo AM, Mir KB, Fazli AA, et al. Exosomes Harnessed as Nanocarriers for Cancer Therapy - Current Status and Potential for Future Clinical Applications. Curr Mol Med. 2021; 21(9): 707-723.
36. de Freitas RCC, Hirata RDC, Hirata MH, Aikawa E. Circulating Extracellular Vesicles As Biomarkers and Drug Delivery Vehicles in Cardiovascular Diseases. Biomolecules. 2021; 11(3): 388.
37. Tian C, Yang Y, Bai B, Wang S, Liu M, Sun RC, et al. Potential of exosomes as diagnostic biomarkers and therapeutic carriers for doxorubicin-induced cardiotoxicity. Int J Biol Sci. 2021; 17(5): 1328-1338.
38. Yarana C, Carroll D, Chen J, Chaiswing L, Zhao Y, Noel T, et al. Extracellular Vesicles Released by Cardiomyocytes in a Doxorubicin-Induced Cardiac Injury Mouse Model Contain Protein Biomarkers of Early Cardiac Injury. Clin Cancer Res. 2018; 24(7): 1644-1653.
39. Zhu Y, Gius D. Glycogen Phosphorylase: A Novel Biomarker in Doxorubicin-Induced Cardiac Injury. Clin Cancer Res. 2018; 24(7): 1516-1517.
40. Beaumier A, Robinson SR, Robinson N, Lopez KE, Meola DM, Barber LG, et al. Extracellular vesicular microRNAs as potential biomarker for early detection of doxorubicin-induced cardiotoxicity. J Vet Intern Med. 2020; 34(3): 1260-1271.
41. Li B, Cai X, Wang Y, Zhu H, Zhang P, Jiang P, et al. Circ-SKA3 Enhances Doxorubicin Toxicity in AC16 Cells Through miR-1303/TLR4 Axis. Int Heart J. 2021; 62(5): 1112-1123.
42. Pudil R, Mueller C, Čelutkienė J, Henriksen PA, Lenihan D, Dent S, et al. Role of serum biomarkers in cancer patients receiving cardiotoxic cancer therapies: a position statement from the Cardio-Oncology Study Group of the Heart Failure Association and the Cardio-Oncology Council of the European Society of Cardiology. Eur J Heart Fail. 2020; 22(11): 1966-1983.