Skip to main content

Advertisement

SpringerLink
Log in

Research progress of biomarkers in early detection of chemotherapy-induced cardiotoxicity

  • Published:
Heart Failure Reviews Aims and scope Submit manuscript

Abstract

With the advances of drug therapy, the prognosis of cancer patients has seen remarkable improvements, and cancer-related mortality has decreased significantly. However, the followed drug-related cardiotoxicity becomes a serious threat to patients’ living quality and survival rate. Cardiovascular toxicity associated with some chemotherapy drugs is reversible and dose-dependent. If early identification is possible, early cardiovascular protection measures or adjustment of chemotherapy regimens can be taken to improve the prognosis of patients. Therefore, early prevention and monitoring of chemotherapy-related cardiotoxicity are critical for cancer patients and survivors. Among them, biomarkers are an important method for the early identification of myocardial injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Truong J, Yan AT, Cramarossa G, Chan KK (2014) Chemotherapy-induced cardiotoxicity: detection, prevention, and management.[J]. Can J Cardiol 30(8):869–878

    Article  PubMed  Google Scholar 

  2. Mertens AC, Liu Q, Neglia JP, Wasilewski K, Leisenring W, Armstrong GT, Robison LL, Yasui Y (2008) Cause-specific late mortality among 5-year survivors of childhood cancer: the childhood cancer survivor study.[J]. J Natl Cancer Inst 100(19):1368–1379

    Article  PubMed  PubMed Central  Google Scholar 

  3. Plana JC, Galderisi M, Barac A, Ewer MS, Ky B, Scherrer-Crosbie M, Ganame J, Sebag IA, Agler DA, Badano LP, Banchs J, Cardinale D, Carver J, Cerqueira M, DeCara J, Edvardsen T, Flamm SD, Force T, Griffin BP, Jerusalem G, Liu JE, Magalhães A, Marwick T, Sanchez LY, Sicari R, Villarraga HR, Lancellotti P (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[J]. Eur Heart J Cardiovasc Imaging 15(10):1063–1093

    Article  PubMed  PubMed Central  Google Scholar 

  4. Cardinale D, Colombo A, Lamantia G, Colombo N, Civelli M, de Giacomi G, Rubino M, Veglia F, Fiorentini C, Cipolla CM (2010) Anthracycline-induced cardiomyopathy: clinical relevance and response to pharmacologic therapy[J]. J Am Coll Cardiol 55(3):213–220

    Article  CAS  PubMed  Google Scholar 

  5. Bird BRJH, Swain SM (2008) Cardiac toxicity in breast cancer survivors: review of potential cardiac problems[J]. Clin Cancer Res 14(1):14–24

    Article  CAS  PubMed  Google Scholar 

  6. Jensen BV, Skovsgaard T, Nielsen SL (2002) Functional monitoring of anthracycline cardiotoxicity: a prospective, blinded, long-term observational study of outcome in 120 patients[J]. Ann Oncol 13(5):699–709

    Article  CAS  PubMed  Google Scholar 

  7. Ky B, Putt M, Sawaya H, French B, Januzzi JL Jr, Sebag IA, Plana JC, Cohen V, Banchs J, Carver JR, Wiegers SE, Martin RP, Picard MH, Gerszten RE, Halpern EF, Passeri J, Kuter I, Scherrer-Crosbie M (2014) Early increases in multiple biomarkers predict subsequent cardiotoxicity in patients with breast cancer treated with doxorubicin, taxanes, and trastuzumab[J]. J Am Coll Cardiol 63(8):809–816

    Article  CAS  PubMed  Google Scholar 

  8. Zardavas D, Suter TM, Van Veldhuisen DJ et al (2017) Role of troponins I and T and N-terminal prohormone of brain natriuretic peptide in monitoring cardiac safety of patients with early-stage human epidermal growth factor receptor 2–positive breast cancer receiving trastuzumab: a herceptin adjuvant study cardiac marker substudy[J]. J Clin Oncol 35(8):878–884

    Article  CAS  PubMed  Google Scholar 

  9. Simões R, Silva LM, Cruz ALVM, Fraga VG, de Paula Sabino A, Gomes KB (2018) Troponin as a cardiotoxicity marker in breast cancer patients receiving anthracycline-based chemotherapy: a narrative review[J]. Biomed Pharmacother 107:989–996

    Article  PubMed  CAS  Google Scholar 

  10. Ponde N, Bradbury I, Lambertini M et al (2017) Cardiac biomarkers for early detection and prediction of trastuzumab and/or lapatinib-induced cardiotoxicity in patients with HER2-positive early-stage breast cancer: a NeoALTTO sub-study (BIG 1–06).[J]. Breast Cancer Res Treat:1–8

  11. Armenian SH, Gelehrter SK, Vase T, Venkatramani R, Landier W, Wilson KD, Herrera C, Reichman L, Menteer JD, Mascarenhas L, Freyer DR, Venkataraman K, Bhatia S (2014) Screening for cardiac dysfunction in anthracycline-exposed childhood cancer survivors.[J]. Clin Cancer Res 20(24):6314–6323

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sherief LM, Kamal AG, Khalek EA et al (2012) Biomarkers and early detection of late onset anthracycline-induced cardiotoxicity in children[J]. Hematology 17(3):151–156

    Article  CAS  PubMed  Google Scholar 

  13. Sawaya H, Sebag IA, Plana JC, Januzzi JL, Ky B, Cohen V, Gosavi S, Carver JR, Wiegers SE, Martin RP, Picard MH, Gerszten RE, Halpern EF, Passeri J, Kuter I, Scherrer-Crosbie M (2011) Early detection and prediction of cardiotoxicity in chemotherapy-treated patients.[J]. Am J Cardiol 107(9):1375–1380

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kitayama H, Kondo T, Sugiyama J, Kurimoto K, Nishino Y, Kawada M, Hirayama M, Tsuji Y (2017) High-sensitive troponin T assay can predict anthracycline- and trastuzumab-induced cardiotoxicity in breast cancer patients.[J]. Breast Cancer 24(6):774–782

    Article  PubMed  Google Scholar 

  15. Mladosievicova B, Urbanova D, Radvanska E et al (2012) Role of NT-proBNP in detection of myocardial damage in childhood leukemia survivors treated with and without anthracyclines[J]. J Exp Clin Cancer Res 31(1):86

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Lenihan DJ, Stevens PL, Massey M, Plana JC, Araujo DM, Fanale MA, Fayad LE, Fisch MJ, Yeh ET (2016) The utility of point-of-care biomarkers to detect cardiotoxicity during anthracycline chemotherapy: a feasibility study[J]. J Card Fail 22(6):433–438

    Article  CAS  PubMed  Google Scholar 

  17. Putt M, Hahn VS, Januzzi JL et al (2015) Longitudinal changes in multiple biomarkers are associated with cardiotoxicity in breast cancer patients treated with doxorubicin, taxanes, and trastuzumab[J]. J Am Coll Cardiol 65(10):1164–1172

    Article  Google Scholar 

  18. Leger KJ, Leonard D, Nielson D et al (2017) Circulating microRNAs: potential markers of cardiotoxicity in children and young adults treated with anthracycline chemotherapy[J]. J Am Heart Assoc 6(4):e004653

    Article  PubMed  PubMed Central  Google Scholar 

  19. Holmgren G, Synnergren J, Andersson CX et al (2016) MicroRNAs as potential biomarkers for doxorubicin-induced cardiotoxicity[J]. Toxicol In Vitro 34(1):26–34

  20. Ruggeri C, Gioffré S, Achilli F, Colombo GI, D'Alessandra Y (2018) Role of microRNAs in doxorubicin-induced cardiotoxicity: an overview of preclinical models and cancer patients[J]. Heart Fail Rev 23(1):109–122

    Article  CAS  PubMed  Google Scholar 

  21. Liang S, Xinyong C, Hongmin Z et al (2018) TLR2 and TLR3 expression as a biomarker for the risk of doxorubicin-induced heart failure[J]. Toxicol Lett

  22. Frères P, Bouznad N, Servais L, Josse C, Wenric S, Poncin A, Thiry J, Moonen M, Oury C, Lancellotti P, Bours V, Jerusalem G (2018) Variations of circulating cardiac biomarkers during and after anthracycline-containing chemotherapy in breast cancer patients[J]. BMC Cancer 18(1):102

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Sawaya H, Sebag IA, Plana JC et al (2012) Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab.[J]. Circ Cardiovasc Imaging 5(5):596

    Article  PubMed  PubMed Central  Google Scholar 

  24. Finkelman BS, Putt M, Wang T et al (2017) Arginine-nitric oxide metabolites and cardiac dysfunction in patients with breast cancer[J]. J Am Coll Cardiol 70(2):152

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Yarana C, Carroll D, Chen J, et al (2017) Extracellular vesicles released by cardiomyocytes in a doxorubicin-induced cardiac injury mouse model contain protein biomarkers of early cardiac injury.[J]. Clin Cancer Res, 112:clincanres.2046.2017

  26. Scuric Z, Carroll JE, Bower JE et al (2017) Biomarkers of aging associated with past treatments in breast cancer survivors[J]. NPJ Breast Cancer 3(1):50

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Balduzzi S, Mantarro S, Guarneri V, Tagliabue L, Pistotti V, Moja L, D’Amico R (2014) Trastuzumab-containing regimens for metastatic breast cancer. In: Moja L (ed) Cochrane Database of Systematic Reviews. John Wiley & Sons, Ltd., Chichester

    Google Scholar 

  28. Morris PG, Chen C, Steingart R et al (2011) Troponin I and C-reactive protein are commonly detected in patients with breast cancer treated with dose-dense chemotherapy incorporating trastuzumab and lapatinib[J]. Clin Cancer Res 17(10):3490–3499

    Article  CAS  PubMed  Google Scholar 

  29. Elghandour AH, Sorady ME, Sahar A et al (2009) Human heart-type fatty acid-binding protein as an early diagnostic marker of doxorubicin cardiac toxicity[J]. Hematol Rev 1(1):543–543

    Google Scholar 

  30. Horacek JM, Jebavy L, Vasatova M, Pudil R, Tichy M, Jakl M, Maly J (2013) Glycogen phosphorylase BB as a potential marker of cardiac toxicity in patients treated with anthracyclines for acute leukemia[J]. Bratisl Med J 114(12):708–710

  31. Hamm CW, Goldmann BU, Heeschen C, Kreymann G, Berger J, Meinertz T (1997) Emergency room triage of patients with acute chest pain by means of rapid testing for cardiac troponin T or troponin I.[J]. N Engl J Med 337(23):1648–1653

    Article  CAS  PubMed  Google Scholar 

  32. Adriana A, Giuseppina P, Francesco D et al (2010) Cardiotoxicity of anticancer drugs: the need for cardio-oncology and cardio-oncological prevention[J]. J Natl Cancer Inst 102(1):14–25

    Article  CAS  Google Scholar 

  33. Kang Y, Xu X, Cheng L, Li L, Sun M, Chen H, Pan C, Shu X (2014) Two-dimensional speckle tracking echocardiography combined with high-sensitive cardiac troponin T in early detection and prediction of cardiotoxicity during epirubicine-based chemotherapy[J]. Eur J Heart Fail 16(3):300–308

    Article  CAS  PubMed  Google Scholar 

  34. Weber M, Hamm C (2006) Role of B-type natriuretic peptide (BNP) and NT-proBNP in clinical routine[J]. Heart 92(6):843–849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. De IF, Salerno G, Taglieri L et al (2016) Serum biomarkers evaluation to predict chemotherapy-induced cardiotoxicity in breast cancer patients.[J]. Tumor Biol 37(3):3379–3387

    Article  CAS  Google Scholar 

  36. Ruggiero A, De Rosa G, Rizzo D et al (2013) Myocardial performance index and biochemical markers for early detection of doxorubicin-induced cardiotoxicity in children with acute lymphoblastic leukaemia[J]. Int J Clin Oncol 18(5):927–933

    Article  CAS  PubMed  Google Scholar 

  37. Christenson ES, James T, Agrawal V, Park BH (2015) Use of biomarkers for the assessment of chemotherapy-induced cardiac toxicity[J]. Clin Biochem 48(4–5):223–235

    Article  CAS  PubMed  Google Scholar 

  38. Vejpongsa P, Yeh ET (2014) Prevention of anthracycline-induced cardiotoxicity: challenges and opportunities[J]. J Am Coll Cardiol 64(9):938–945

    Article  CAS  PubMed  Google Scholar 

  39. Eulalio A, Huntzinger E, Izaurralde E (2008) Getting to the root of miRNA-mediated gene silencing.[J]. Cell 132(1):9–14

    Article  CAS  PubMed  Google Scholar 

  40. Kapranov P, Cheng J, Dike S, Nix DA, Duttagupta R, Willingham AT, Stadler PF, Hertel J, Hackermüller J, Hofacker IL, Bell I, Cheung E, Drenkow J, Dumais E, Patel S, Helt G, Ganesh M, Ghosh S, Piccolboni A, Sementchenko V, Tammana H, Gingeras TR (2007) RNA maps reveal new RNA classes and a possible function for pervasive transcription.[J]. Science 316(5830):1484–1488

    Article  CAS  PubMed  Google Scholar 

  41. Yi X, Bekeredjian R, DeFilippis NJ, Siddiquee Z, Fernandez E, Shohet RV (2006) Transcriptional analysis of doxorubicin-induced cardiotoxicity.[J]. Am J Physiol Heart Circ Physiol 290(3):1098–1102

    Article  CAS  Google Scholar 

  42. Riad A, Bien S, Gratz M et al (2014) Toll-like receptor-4 deficiency attenuates doxorubicin-induced cardiomyopathy in mice.[J]. Eur J Heart Fail 10(3):233–243

    Article  CAS  Google Scholar 

  43. Frantz S, Kelly RA, Bourcier T (2001) Role of TLR-2 in the activation of nuclear factor kappaB by oxidative stress in cardiac myocytes.[J]. J Biol Chem 276(7):5197–5203

    Article  CAS  PubMed  Google Scholar 

  44. Boxtel WV, Bulten BF, Mavinkurve-Groothuis AMC et al (2015) New biomarkers for early detection of cardiotoxicity after treatment with docetaxel, doxorubicin and cyclophosphamide[J]. 20(2):143

  45. Sharma A, Khatun Z, Shiras A (2016) Tumor exosomes: cellular postmen of cancer diagnosis and personalized therapy[J]. Nanomedicine 11(4):421–437

    Article  CAS  PubMed  Google Scholar 

  46. Jih-Kai Y, Chao-Yung W (2016) Telomeres and telomerase in cardiovascular diseases[J]. Genes 7(9):58

    Article  CAS  Google Scholar 

  47. (2011) Telomere length in old age and cholesterol across the life course[J]. J Am Geriatr Soc 59(10):1979–1981

  48. Beyer AM, Freed JK, Durand MJ, Riedel M, Ait-Aissa K, Green P, Hockenberry JC, Morgan RG, Donato AJ, Peleg R et al (2016) Critical role for telomerase in the mechanism of flow-mediated dilation in the human microcirculation. Circ Res 118:856–866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Shrivastava AK, Singh HV, Raizada A, Singh SK (2015) C-reactive protein, inflammation and coronary heart disease. Egypt Heart J 67:89–97

    Article  Google Scholar 

  50. Christenson ES, James T, Agrawal V et al (2014) Use of biomarkers for the assessment of chemotherapy-induced cardiac toxicity[J]. Clin Biochem 48(4–5)

  51. Xia Z (2018) Heart-type fatty acid binding protein (H-FABP) as a biomarker for acute myocardial injury and long-term post-ischemic prognosis[J]. Acta Pharmacol Sin 39(7)

  52. Keller T, Zeller T, Ojeda F et al (2011) Serial changes in highly sensitive troponin I assay and early diagnosis of myocardial infarction[J]. JAMA 306(24):2684–2693

  53. Lillpopp L , Tzikas S , Ojeda F et al (2012) Prognostic information of glycogen phosphorylase isoenzyme BB in patients with suspected acute coronary syndrome[J]. Am J Cardiol 110(9):1225–1230

Download references

Funding

This study was funded by the basic applied research projects in Shanxi Province (grant number 201601D021156) and the Scientific Research Fund of Shanxi cardiovascular Hospital (grant number 20170203) and the Scientific Research Topics of Shanxi Health commission (grant number 2015070).

Author information

Author notes

  1. Wanli Gai and Jian An contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan, 030024, Shanxi, People’s Republic of China

    Wanli Gai, Jian An, Zhixin Wang, Xuebin Han, Jianhui Geng & Yanqing Guo

  2. Department of Cardiovascular Medicine, First Hospital of Shanxi Medical University, Taiyuan, 030001, Shanxi, People’s Republic of China

    Yunliang Liang

Authors
  1. Wanli Gai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jian An
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Zhixin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xuebin Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jianhui Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yunliang Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Yanqing Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yanqing Guo.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gai, W., An, J., Wang, Z. et al. Research progress of biomarkers in early detection of chemotherapy-induced cardiotoxicity. Heart Fail Rev 26, 1195–1201 (2021). https://doi.org/10.1007/s10741-020-09948-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10741-020-09948-6

Keywords

Search

Navigation