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Cardiovascular Toxicology

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01.06.2007 | Original Paper

Genotyping the risk of anthracycline-induced cardiotoxicity

verfasst von: Shiwei Deng, Leszek Wojnowski

Erschienen in: Cardiovascular Toxicology | Ausgabe 2/2007

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Abstract

Anthracyclines belong to the most successful antineoplastic drugs, but they are cardiotoxic, which may result in congestive heart failure (CHF). The CHF risk increases with the cumulative anthracycline dose, but it seems also to be modified by individual factors. A role of the individual genetic background is consistent with the altered sensitivity to anthracyclines observed in many transgenic and knockout mouse strains. First clinical data obtained in humans suggest the existence of predisposing variants in genes involved in the oxidative stress, and in the metabolism and transport of anthracyclines. These data will have to be verified in further clinical trials before any attempts of their application in the individual cardiotoxicity prediction can be undertaken. In the meantime, anthracycline-induced cardiotoxicity can be best reduced by application of liposomal anthracycline formulations or by a co-medication with the cardioprotective iron chelator dexrazoxane.

Friedman, M. A., Bozdech, M. J., Billingham, M. E., & Rider, A. K. (1978). Doxorubicin cardiotoxicity. Serial endomyocardial biopsies and systolic time intervals. Jama, 240, 1603–1606.PubMedCrossRef

Steinberg, J. S., Cohen, A. J., Wasserman, A. G., Cohen, P., & Ross, A. M. (1987). Acute arrhythmogenicity of doxorubicin administration. Cancer, 60, 1213–1218.PubMedCrossRef

Von Hoff, D. D., Layard, M. W., Basa, P., Davis, H. L Jr, Von Hoff, A. L., Rozencweig, M., & Muggia, F. M. (1979). Risk factors for doxorubicin-induced congestive heart failure. Annals of Internal Medicine, 91, 710–717.

van Dalen, E. C., van der Pal, H. J., Kok, W. E., Caron, H. N., & Kremer, L. C. (2006). Clinical heart failure in a cohort of children treated with anthracyclines: a long-term follow-up study. European Journal of Cancer, 42, 3191–3198.PubMedCrossRef

Swain, S. M., Whaley, F. S., & Ewer, M. S. (2003). Congestive heart failure in patients treated with doxorubicin: a retrospective analysis of three trials. Cancer, 97, 2869–2879.PubMedCrossRef

Lipshultz, S. E., Colan, S. D., Gelber, R. D., Perez-Atayde, A. R., Sallan, S. E., & Sanders, S. P. (1991). Late cardiac effects of doxorubicin therapy for acute lymphoblastic leukemia in childhood. The New England Journal of Medicine, 324, 808–815.PubMedCrossRef

Wouters, K. A., Kremer, L. C., Miller, T. L., Herman, E. H., & Lipshultz, S. E. (2005). Protecting against anthracycline-induced myocardial damage: a review of the most promising strategies. British Journal of Haematology, 131, 561–578.PubMedCrossRef

Otterness, D., Szumlanski, C., Lennard, L., Klemetsdal, B., Aarbakke, J., Park-Hah, J. O., Iven, H., Schmiegelow, K., Branum, E., O’Brien, J., & Weinshilboum, R. (1997). Human thiopurine methyltransferase pharmacogenetics: gene sequence polymorphisms. Clinical Pharmacology and Therapeutics, 62, 60–73.PubMedCrossRef

Yates, C. R., Krynetski, E. Y., Loennechen, T., Fessing, M. Y., Tai, H. L., Pui, C. H., Relling, M. V., & Evans, W. E. (1997). Molecular diagnosis of thiopurine S-methyltransferase deficiency: genetic basis for azathioprine and mercaptopurine intolerance. Annals of Internal Medicine, 126, 608–614.PubMed

10.

Evans, W. E., Hon, Y. Y., Bomgaars, L., Coutre, S., Holdsworth, M., Janco, R., Kalwinsky, D., Keller, F., Khatib, Z., Margolin, J., Murray, J., Quinn, J., Ravindranath, Y., Ritchey, K., Roberts, W., Rogers, Z. R., Schiff, D., Steuber, C., Tucci, F., Kornegay, N., Krynetski, E. Y., & Relling, M. V. (2001). Preponderance of thiopurine S-methyltransferase deficiency and heterozygosity among patients intolerant to mercaptopurine or azathioprine. Journal of Clinical Oncology, 19, 2293–2301.PubMed

11.

Schutz, E., Gummert, J., Mohr, F., & Oellerich, M. (1993). Azathioprine-induced myelosuppression in thiopurine methyltransferase deficient heart transplant recipient. Lancet, 341, 436.PubMedCrossRef

12.

Wang, L., & Weinshilboum, R. (2006). Thiopurine S-methyltransferase pharmacogenetics: insights, challenges and future directions. Oncogene, 25, 1629–1638.PubMedCrossRef

13.

Haga, S. B., Thummel, K. E., & Burke, W. (2006). Adding pharmacogenetics information to drug labels: lessons learned. Pharmacogenet Genomics, 16, 847–854.PubMed

14.

Dell’Acqua, G., Polishchuck, R., Fallon, J. T., & Gordon, JW. (1999). Cardiac resistance to adriamycin in transgenic mice expressing a rat alpha-cardiac myosin heavy chain/human multiple drug resistance 1 fusion gene. Human Gene Therapy, 10, 1269–1279.PubMedCrossRef

15.

Olson, L. E., Bedja, D., Alvey, S. J., Cardounel, A. J., Gabrielson, K. L., & Reeves, R. H. (2003). Protection from doxorubicin-induced cardiac toxicity in mice with a null allele of carbonyl reductase 1. Cancer Research, 63, 6602–6606.PubMed

16.

Forrest, G. L., Gonzalez, B., Tseng, W., Li, X., & Mann, J. (2000). Human carbonyl reductase overexpression in the heart advances the development of doxorubicin-induced cardiotoxicity in transgenic mice. Cancer Research, 60, 5158–5164.PubMed

17.

Paulides, M., Kremers, A., Stohr, W., Bielack, S., Jurgens, H., Treuner, J., Beck, J. D., & Langer, T. (2006). German Late Effects Working Group in the Society of Pediatric Oncology, Haematology (GPOH). Prospective longitudinal evaluation of doxorubicin-induced cardiomyopathy in sarcoma patients: a report of the late effects surveillance system (LESS). Pediatric Blood and Cancer, 46, 489–495.PubMedCrossRef

18.

Henderson, I. C., Allegra, J. C., Woodcock, T., Wolff, S., Bryan, S., Cartwright, K., Dukart, G., & Henry, D. (1989). Randomized clinical trial comparing mitoxantrone with doxorubicin in previously treated patients with metastatic breast cancer. J Clin Oncol, 7, 560–571.PubMed

19.

Aplenc, R., Blanco, J., Leiisenring, W., Davies, S., Relling, M., Robinson, L., Sklar, C., Stovall, M., & Bathia, S. (2006). Polymorphisms in candidate genes in patients with congestive heart failure (CHF) after childhood cancer: A report from the Childhood Cancer Survivor Study (CCSS). Journal of Clinical Oncology, 2418S, 9004A.

20.

Wojnowski, L., Kulle, B., Schirmer, M., Schluter, G., Schmidt, A., Rosenberger, A., Vonhof, S., Bickeboller, H., Toliat, M. R., Suk, E. K., Tzvetkov, M., Kruger, A., Seifert, S., Kloess, M., Hahn, H., Loeffler, M., Nurnberg, P., Pfreundschuh, M., Trumper, L., Brockmoller, J., & Hasenfuss, G. (2005). NADPH oxidase and multidrug resistance protein genetic polymorphisms are associated with doxorubicin-induced cardiotoxicity. Circulation, 112, 3754–3762.PubMedCrossRef

21.

Heymes, C., Bendall, J. K., Ratajczak, P., Cave, A. C., Samuel, J. L., Hasenfuss, G., & Shah, A. M. (2003). Increased myocardial NADPH oxidase activity in human heart failure. Journal of the American College of Cardiology, 41, 2164–2171.PubMedCrossRef

22.

Soccio, M., Toniato, E., Evangelista, V., Carluccio, M., & De Caterina, R. (2005). Oxidative stress and cardiovascular risk: the role of vascular NADPH oxidase and its genetic variants. European Journal of Clinical Investigation, 35, 305–314.PubMedCrossRef

23.

Deng, S., Kruger, A., Kleschyov, A. L., Kalinowski, L., Daiber, A., Wojnowski, L. (2007). Gp91phox-containing NADPH oxidase increases superoxide formation by doxorubicin and NADPH. Journal of Free Radical Biology and Medicine, 42, 466–473.

24.

Bartoszek, A., & Wolf, C. R. (1992). Enhancement of doxorubicin toxicity following activation by NADPH cytochrome P450 reductase. Biochemical Pharmacology, 43, 1449–1457.PubMedCrossRef

25.

Vasquez-Vivar, J., Martasek, P., Hogg, N., Masters, B. S., Pritchard, K. A Jr, & Kalyanaraman, B. (1997). Endothelial nitric oxide synthase-dependent superoxide generation from adriamycin. Biochemistry, 36, 11293–11297.PubMedCrossRef

26.

Doroshow, J. H. (1983). Anthracycline antibiotic-stimulated superoxide, hydrogen peroxide, and hydroxyl radical production by NADH dehydrogenase. Cancer Research, 43, 4543–4551.PubMed

27.

van Dalen, E. C., Caron, H. N., Dickinson, H. O., & Kremer, L. C. (2005). Cardioprotective interventions for cancer patients receiving anthracyclines. Cochrane Database of Systematic Reviews, 1, CD003917.

28.

Cole, S. P., Bhardwaj, G., Gerlach, J. H., Mackie, J. E., Grant, C. E., Almquist, K. C., Stewart, A. J., Kurz, E. U., Duncan, A. M., & Deeley, R. G. (1992). Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science, 258, 1650–1654.PubMedCrossRef

29.

Cui, Y., Konig, J., Buchholz, J. K., Spring, H., Leier, I., & Keppler, D. (1999). Drug resistance and ATP-dependent conjugate transport mediated by the apical multidrug resistance protein, MRP2, permanently expressed in human and canine cells. Molecular Pharmacology, 55, 929–937.PubMed

30.

Flens, M. J., Zaman, G. J., van der Valk P., Izquierdo, M. A., Schroeijers, A. B., Scheffer, G. L., van der Groep, P., de Haas, M., Meijer, C. J., & Scheper, R. J. (1997). Tissue distribution of the multidrug resistance protein. The American Journal of Pathology, 148, 1237–1247.

31.

Wijnholds, J., Evers, R., van Leusden, M. R., Mol, C. A., Zaman, G. J., Mayer, U., Beijnen, J. H., van der Valk, M., Krimpenfort, P., & Borst, P. (1997). Increased sensitivity to anticancer drugs and decreased inflammatory response in mice lacking the multidrug resistance-associated protein. Nature Medicine, 3, 1275–1279.PubMedCrossRef

32.

Rajagopal, A., & Simon, S. M. (2003). Subcellular localization and activity of multidrug resistance proteins. Molecular Biology of the Cell, 14, 3389–3399.PubMedCrossRef

33.

Hidemura, K., Zhao, Y. L., Ito, K., Nakao, A., Tatsumi, Y., Kanazawa, H., Takagi, K., Ohta, M., & Hasegawa, T. (2003). Shiga-like toxin II impairs hepatobiliary transport of doxorubicin in rats by down-regulation of hepatic P glycoprotein and multidrug resistance-associated protein Mrp2. Antimicrobial Agents and Chemotherapy, 47, 1636–1642.PubMedCrossRef

34.

Jacquet, J. M., Bressolle, F., Galtier, M., Bourrier, M., Donadio, D., Jourdan, J., & Rossi, J. F. (1990). Doxorubicin and doxorubicinol: intra- and inter-individual variations of pharmacokinetic parameters. Cancer Chemotherapy and Pharmacology, 27, 219–225.PubMedCrossRef

35.

Piscitelli, S. C., Rodvold, K. A., Rushing, D. A., & Tewksbury, D. A. (1993). Pharmacokinetics and pharmacodynamics of doxorubicin in patients with small cell lung cancer. Clinical Pharmacology and Therapeutics, 53, 555–561.PubMedCrossRef

36.

Yen, H. C., Oberley, T. D., Vichitbandha, S., Ho, Y. S., & St Clair, D. K. (1996). The protective role of manganese superoxide dismutase against adriamycin-induced acute cardiac toxicity in transgenic mice. The Journal of Clinical Investigation, 98, 1253–1260.PubMedCrossRef

37.

Kang, Y. J., Chen, Y., & Epstein, P. N. (1996). Suppression of doxorubicin cardiotoxicity by overexpression of catalase in the heart of transgenic mice. The Journal of Biological Chemistry, 271, 12610–12616.PubMedCrossRef

38.

Badary, O. A., Awad, A. S., Abdel-Maksoud, S., & Hamada, F. M. (2004). Cardiac DT-diaphorase contributes to the detoxification system against doxorubicin-induced positive inotropic effects in guinea-pig isolated atria. Clinical and Experimental Pharmacology and Physiology, 31, 856–861.PubMedCrossRef

39.

Gutierrez, P. L. (2000). The role of NADPH oxidoreductase (DT-Diaphorase) in the bioactivation of quinone-containing antitumor agents: a review. Free Radical Biology and Medicine, 29, 263–275.PubMedCrossRef

40.

L’Ecuyer, T., Allebban, Z., Thomas, R., & Vander Heide, R. (2004). Glutathione S-transferase overexpression protects against anthracycline-induced H9C2 cell death. American Journal of Physiology. Heart and Circulatory Physiology, 286, H2057–2064.PubMedCrossRef

41.

Harbottle, A., Daly, A. K., Atherton, K., & Campbell, F. C. (2001). Role of glutathione S-transferase P1, P-glycoprotein and multidrug resistance-associated protein 1 in acquired doxorubicin resistance. International Journal of Cancer, 92, 777–783.CrossRef

42.

Wang, K., Ramji, S., Bhathena, A., Lee, C., & Riddick, D. S. (1999). Glutathione S-transferases in wild-type and doxorubicin-resistant MCF-7 human breast cancer cell lines. Xenobiotica, 29, 155–170.PubMedCrossRef

43.

Gaudiano, G., Koch, T. H., Lo Bello, M., Nuccetelli, M., Ravagnan, G., Serafino, A., & Sinibaldi-Vallebona, P. (2000). Lack of glutathione conjugation to adriamycin in human breast cancer MCF-7/DOX cells. Inhibition of glutathione S-transferase p1–1 by glutathione conjugates from anthracyclines. Biochemical Pharmacology, 60, 1915–1923.PubMedCrossRef

44.

Herbert, A., Gerry, N. P., McQueen, M. B., Heid, I. M., Pfeufer, A., Illig, T., Wichmann, H. E., Meitinger, T., Hunter, D., Hu, F. B., Colditz, G., Hinney, A., Hebebrand, J., Koberwitz, K., Zhu, X., Cooper, R., Ardlie, K., Lyon, H., Hirschhorn, J. N., Laird, N. M., Lenburg, M. E., Lange, C., & Christman, M. F. (2006). A common genetic variant is associated with adult and childhood obesity. Science, 312, 279–283.PubMedCrossRef

45.

van Dalen, E. C., Michiels, E. M., Caron, H. N., & Kremer, L. C. (2006). Different anthracycline derivates for reducing cardiotoxicity in cancer patients. Cochrane Database of Systematic Reviews, 4, CD005006.

46.

Moghrabi, A., Levy, D. E., Asselin, B., Barr, R., Clavell, L., Hurwitz, C., Samson, Y., Schorin, M., Dalton, V. K., Lipshultz, S. E., Neuberg, D. S., Gelber, R. D., Cohen, H. J., Sallan, S. E., & Silverman, L. B. (2007). Results of the Dana-Farber Cancer Institute ALL Consortium Protocol 95-01 for children with acute lymphoblastic leukemia. Blood, 109, 896–904.PubMedCrossRef

47.

Marty, M., Espie, M., Llombart, A., Monnier, A., Rapoport, B. L., & Stahalova, V. (2006). Dexrazoxane Study Group. Multicenter randomized phase III study of the cardioprotective effect of dexrazoxane (Cardioxane) in advanced/metastatic breast cancer patients treated with anthracycline-based chemotherapy. Annals of Oncology, 17, 614–622.PubMedCrossRef

Titel: Genotyping the risk of anthracycline-induced cardiotoxicity
verfasst von: Shiwei Deng
Leszek Wojnowski
Publikationsdatum: 01.06.2007
Verlag: Humana Press Inc
Erschienen in: Cardiovascular Toxicology / Ausgabe 2/2007
Print ISSN: 1530-7905
Elektronische ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-007-0024-2

Springer Medizin

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