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Multidrug resistance in pediatric oncology

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Summary

Cancer survival among children and adolescents has improved markedly due to evolution of multimodal treatment that incorporates combination chemotherapy, radiation therapy and/or surgery. However, 20–30% of children with malignancies will succumb to their disease or complications associated with their disease or treatment. A major limiting factor to improvement in survival among these patients is the occurrence of intrinsic and/or acquired resistance to our treatment interventions, chemotherapy and radiotherapy. Among these mechanisms, multidrug resistance, the focus of this review, is a well-documented phenomenon whose biochemistry, pharmacology and molecular biology has been extensively studied. A role for multidrug resistance in chemoresistance and therapeutic failure in childhood malignancies is suggested by the observation of clinical resistance to treatment regimes containing agents that are known substrates of multidrug resistance mechanisms. With the current results from studies in rhabdomyosarcoma, neuroblastoma, osteosarcoma, Ewing's sarcoma, leukemia and retinoblastoma, the role of multidrug resistance is still unclear. Earlier studies attempted to define a role for P-glycoprotein-mediated multidrug resistance; however, a limited number of reports suggest that the multidrug-associated resistance protein may play an active role in neuroblastoma. Further studies will be necessary using standardized and uniform approaches for the analyses of these mechanisms. Clinical trials directed toward reversal of multidrug resistance are premature since the exact role of P-glycoprotein is controversial in pediatric malignancies, the role of other mechanisms of multidrug resistance must be assessed and selective inhibitors of multidrug resistance have yet to be developed.

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References

  1. Biedler JL, Reihm H: Cellular resistance to actinomycin D in Chinese hamster cells in vitro: cross-resistance, radioautographic and cytogenetic studies. Cancer Res 30:1174–1184, 1970.

    Google Scholar 

  2. Ling V, Thompson LH: Reduced permeability in CHO cells as a mechanism of resistance to colchicine. J Cell Phsyiol 83:103–116, 1974.

    Google Scholar 

  3. Juliano RL, Long V: A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 435:152–162, 1976.

    Google Scholar 

  4. Houghton PJ: Chapter 5. Modulation of p-Glycoprotein-mediated multidrug resistance. In: Tew KD, Houghton PJ, Houghton JA (eds): Preclinical and Clinical Modulation of Anticancer Drugs. CRC Press, Boca Raton, Florida, 1993, pp 125–196.

    Google Scholar 

  5. Juranka PF, Zastawny RL, Ling V: P-glycoprotein: multidrug-resistance and a superfamily of membrane-associated transport proteins. FASEB J 3:2583–2592, 1989.

    Google Scholar 

  6. Cole SPC, Bhardwaj G, Gerlach JH, Mackie JE, Grant CE, Almquist KC, Stewart AJ, Kurz EU, Duncan AMV, Deeley RG: Overexpression of a transporter gene in a multidrug-resistant human lung cancer cell line. Science 258:1650–1654, 1992.

    Google Scholar 

  7. Scheper RJ, Broxterman HJ, Scheffer GL, Kaaijk P, Dalton WS, van Heijningen THM, van Kalken CK, Slovak ML, de Vries EG, Van der Valk P, Meijer C, J.L.M., Pinedo HM: Overexpression of MR 110,000 vesicular protein in non-P-glycoprotein-mediated multidrug resistance. Cancer Res 53:1475–1479, 1993.

    Google Scholar 

  8. Beck WT, Danks MK: Mechanisms of resistance to drugs that inhibit DNA topoisomerases. Semin Cancer Biol 2:235–244, 1991.

    Google Scholar 

  9. Danks M, Yalowich J, Beck W: A typical multiple drug resistance in a human leukemic cell lineselected for resistance to teniposide (VM-26). Cancer Res 47:1297–1302, 1987.

    Google Scholar 

  10. Kartner N, Evernden-Poreile D, Bradley G, Ling V: Detection of P-glycoprotein in multidrug-resistant cell lines by monoclonar antibodies. Nature 316:820, 1985.

    Google Scholar 

  11. Dalton WS, Grogan TM, Rybski JA, Scheper R, Richter L, Kailev J, Broxterman HJ, Pinedo HM, Salmon SE: Immunohistochemical detection and quantification of P-glycoprotein in multiple drug-resistant human myeloma cells: Association with level of drug resistance and drug accumulation. Blood 73:747–752, 1989.

    Google Scholar 

  12. Horton JK, Houghton JA, Houghton PJ: Expression of multidrug resistance gene (MDR1) in human tumor xenografts sensitive and resistant to natural products: failure to predict chemosensitivity. J Cell Pharmacol 2:208–216, 1991.

    Google Scholar 

  13. Shen D, Cardarelli C, Hwang J, Cornwell M, Richert N, Ishii S, Pastan I, Gottesman MM: Multiple drug-resistant human KB carcinoma cells independently selected for high-level resistance to colchicine, adriamycin, or vinblastine show changes in expression of specific proteins. J Biol Chem 261:7762–7770, 1986.

    Google Scholar 

  14. Ueda K, Cardarelli C, Gottesman MM, Pastan I: Expression of a full length cDNA for the human MDR1 gene confers resistance to colchicine, doxorubicin, and vinblastine. Proc Natl Acad Sci USA 84:3004–3008, 1987.

    Google Scholar 

  15. Chan HSL, Thorner P, Haddad G, Ling V: Immunohistochemical detection of P-glycoprotein: prognostic correlation in soft tissue sarcoma of childhood. J Clin Oncol 8:689–704, 1990.

    Google Scholar 

  16. Campos L, Guyotat D, Archimbaud E, Caimara-Orioi P, Tsurao T, Troncy J, Treme D, Fiere D: Clinical significance of multidrug resistance P-glycoprotein expression on acute nonlymphoblastic leukemia cells at diagnosis. Blood 79:473–476, 1992.

    Google Scholar 

  17. Leuschner I, Schmidt D, Hoffmann H, Dietel M, Harms D: Expression of p-glycoprotein in soft tissue tumors of childhood correlation to treatment response. J Cancer Res Clin Oncol 117:510–514, 1993 (abstract).

    Google Scholar 

  18. Favrot M, Combaret V, Goilot E, Wagner JP, Bouffet E, Mazingue F, Thyss A, Bordigoni P, Delsol G, Bailly C, Fontaniere B, Philip T: Expression of p-glycoprotein restricted to normal cells in neuroblastoma biopsies. Br J Cancer 64:233–238, 1991.

    Google Scholar 

  19. Chan HSL, Haddad G, Thorner PS, DeBoer G, Lin YP, Ondrusek N, Yeger H, Ling V: P-glycoprotein expression as a predictor of the outcome of therapy for neuroblastoma. N Engl J Med 325:1608–1614, 1991.

    Google Scholar 

  20. Chaudhary PM, Roninson IB: Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoietic stem cells. Cell 66:85–94, 1991.

    Google Scholar 

  21. Dalton WS, Grogan TM, Meltzer P, Scheper R, Durie BGM, Taylor C, Miller T, Salmon S: Drug-Resistance in Multiple Myeloma and Non-hodgkin's Lymphoma: Detection of P-Glycoprotein and Potential Circumvention by Addition of Verapamil to Chemotherapy. J Clin Oncol 7:415–424, 1989.

    Google Scholar 

  22. Garberoglio C, Dudas M, Casper ES, Bertino J, Cordon-Cardo C: Expression of P-glycoprotein in normal muscle cells and myogenic tumors. Arch Pathol lab Med 116:1055–1061, 1992.

    Google Scholar 

  23. Schlaifer D, Laurent G, Chittal S, Tsuruo T, Soues S, Muller C, Charcosset JY, Alard C, Brousset P, Mazerrolles C, Delsol G: Immunohistochemical detection of multidrug resistance associated P-glycoprotein in tumour and stromal cells of human cancers. Br J Cancer 62:177–182, 1990.

    Google Scholar 

  24. Hegewisch-Becker S, Fliegner M, Tsuruo T, Zander A, Zeller W, Hossfeld DK: P-glycoprotein expression in normal and reactive bone marrows. Br J Cancer 67:430–435, 1993.

    Google Scholar 

  25. Goldstein LJ, Fojo AT, Ueda K, Crist W, Green A, Brodeur G, Pastin I, Gottesman MM: Expression of the multidrug resistance, MDR1, gene in neuroblastomas. J Clin Oncol 8:128–136, 1990.

    Google Scholar 

  26. Goldstein LJ, Galski H, Fojo A, Willingham, Lai S, Gazdar A, Pirker R, Green A, Crist W, Brodeur GM, Lieber M, Cossman J, Gottesman MM, Pastan I: Expression of a multidrug resistance gene in human cancers. J Natl Cancer Inst 81:116–124, 1989.

    Google Scholar 

  27. Marie J, Zittoun R, Sikic BI: Multidrug resistance (mdr-1) gene expression in adult acute leukemias: correlations with treatment outcome and in vitro drug sensitivity. Blood 78:586–592, 1991.

    Google Scholar 

  28. Nakagawara A, Kadomatsu K, Sato S, Kohno K, Takano H, Akazawa K, Nose Y, Kuwano M: Inverse correlation between expression of multidrug resistance gene and N-myc oncogene in human neuroblastomas. Cancer Res 50:3043–3047, 1990.

    Google Scholar 

  29. Noonan KE, Beck C, Holzmayer TA, Chin JE, Wunder JS, Andrulis IL, Gazdar AF, Willman CL, Griffith B, Von Hoff DD, Roninson IB: Quantitative analysis of MDR1 (multidrug resistance) gene expression in human tumors by polymerase chain reaction. Proc Natl Acad Sci USA 87:7160–7164, 1990.

    Google Scholar 

  30. Sato H, Gottesman MM, Goldstein LJ, Pastan I, Block AM, Sandberg AA, Preisler HD: Expression of the multidrug resistance gene in myeloid leukemias. Leukemia Res 14:11–22, 1990.

    Google Scholar 

  31. Thiebaut F, Tsuruo T, Hamada H, Gottesman MM, Pastan I, Willingham MC: Cellular localization of the multidrug-resistance gene product P-glycoprotein in normal human tissues. Proc Natl Acad Sci USA 84:7735–7738, 1987.

    Google Scholar 

  32. Chan HSL, DeBoer G, Haddad G, Gallie BL, Ling V: Multidrug resistance in pediatric malignancies. Hematol Oncol Clin NA 9:275–318, 1995.

    Google Scholar 

  33. Pappo AS, Kuttesch JF, Santana VM, Shapiro DN: Pediatric Tumors, Abeloff MD, Armitage JO, Lichter AS, et al. (eds): Clinical Oncology New York, Churchill Livingstone, Inc. 1995, pp 1847–1887.

    Google Scholar 

  34. Wollman Y, Shahar I, Goldstein M, Leibovici J: Malignant phenotype correlating with drug resistance in two human neuroblastoma cell lines. J Neurooncol 19:123–129, 1994.

    Google Scholar 

  35. Ferrandis E, DaSilva J, Riou G, Benard I: Coactivation of the MDR1 and MYCN genes in human neuroblastoma cells during the metastatic process in the nude mouse. Cancer Res 54:2256–2261, 1994.

    Google Scholar 

  36. LaQuaglia MP, Kopp EB, Spengler BA, Meyers MB, Biedler JL: Multidrug resistance in human neuroblastoma cells. J Pediatr Surg 26:1107–1112, 1991.

    Google Scholar 

  37. Bourhis J, Benard J, Hartmann O, Boccon-Gibod L, Lemerle J, Riou G: Correlation of MDR1 gene expression with chemotherapy in neuroblastoma. J Natl Cancer Inst 81:1401–1405, 1989.

    Google Scholar 

  38. Corrias MV, Cornaglia-Ferraris P, DiMartino D, Stenger AM, Lanino E, Boni L, Tonini GP: Expression of multiple drug resistance gene, MDR1, and N-MYC oncogene in an Italian population of human neuroblastoma patients. Anticancer Res 10:897–902, 1990.

    Google Scholar 

  39. Jessell TM, Kandel ER: Synaptic transmission: a bidirectional and self-modifiable form of cell-cell communication. Cell 72:1–30, 1993.

    Google Scholar 

  40. Ramani R, Dewchand H: Expression of mdr1/P-glycoprotein and p110 in neuroblastoma. J Pathol 175:13–22, 1995.

    Google Scholar 

  41. Bates SE, Shieh CY, Tsokos M: Expression of mdr-1/P-glycoprotein in human neuroblastoma. Am J Pathol 139:305–315, 1991.

    Google Scholar 

  42. O'Meara A, Imamura A, Johnson P, Ball R, Rooney S, Kierce B, Tsuruo T, Dervan P: Reactivity of P-glycoprotein monoclonal antibodies in childhood cancers. Oncology 49:203–208, 1992.

    Google Scholar 

  43. Horton JK, Houghton PJ, Houghton JA: Reciprocal cross-resistance in human rhabdomyosarcomas selected in vivo for primary resistance to vincristine and L-phenylalanine mustard. Cancer Res 47:6288–6293, 1987.

    Google Scholar 

  44. Horton JK, Thimmaiah KN, Harwood FF, Kuttesch JF, Houghton PJ: Pharmacological characterization of N-substituted phenoxazines directed toward reversing vinca alkaloid resistance in multidrug-resistant cancer cells. Mol Pharmacol 44:552–559, 1993.

    Google Scholar 

  45. Chan HSL, DeBoer G, Thorner PS, Haddad G, Gallie BL, Ling V: Multidrug resistance: clinical opportunities in diagnosis and circumvention. Hematol Oncol Clin NA 8:383–410, 1994.

    Google Scholar 

  46. Kuttesch JFJ, Parham DM, Luo X, Meyer WH, Bowman L, Shapiro DN, Pappo AS, Crist WM, Beck WT, Houghton PJ: P-Glycoprotein expression at diagnosis may not be a primary mechanism of therapeutic failure in childhood rhabdomyosarcoma. J Clin Oncol [in press].

  47. McDowell H, Peuchmaur M, Dominici C, Flamant F: Multidrug resistance gene transcript level, and P-glycoprotein expression in paediatric malignant mesenchymal tumours. Anticancer Res 13:1863–1866, 1993.

    Google Scholar 

  48. Chan HSL, Thorner PS, Haddad G, Ling V: Outcome of therapy in osteosarcoma correlates with P-glycoprotein expression. Proc Am Assoc Cancer Res 32:366, 1991 (abstract).

    Google Scholar 

  49. Baldini N, Scotlandi K, Barbanti-Brodano G, Manara MC, Maurici D, Bacci G, Bertoni F, Picci P, Sottili S, Campanacci M, Serra M: Expression of P-glycoprotein in high-grade osteosarcomas in relation to clinical outcome. N Engl J Med 23:1380–1385, 1995.

    Google Scholar 

  50. Pinedo HM, Giaccone G: P-Glycoprotein — a marker of cancer-cell behavior. N Engl J Med 333:1417–1418, 1996.

    Google Scholar 

  51. Roessner A, Ueda Y, Bockhorn-Dworniczak B, Blasius S, Peters A, Wuisman P, Ritter J, Paulussen M, Jurgens H, Bocker W: Prognostic implication of immunodetection of P-glycoprotein in Ewing's sarcoma. J Cancer Res Clin Oncol 119:185–189, 1993.

    Google Scholar 

  52. Chan HSL, Haddad G, Thorner PS, DeBoer G, Long V: P-glycoprotein expression as a predictor of the outcome of therapy for Ewing's sarcoma. Proc Am Assoc Cancer Res 34:1993 (abstract).

  53. Hijazi YM, Axiotis CA, Navarro S, Steinberg SM, Horowitz ME, Tsokos M: Immunohistochemical detection of P-glycoprotein in Ewing's sarcoma and peripheral primative neuroectodermal tumors before and after chemotherapy. Am J Clin Pathol 102:61–67, 1994.

    Google Scholar 

  54. Chan HSL, Canton MD, Gallie BL: Chemosensitivity and multidrug resistance to antineoplastic drugs in retinoblastoma cell lines. Anticancer Res 9:469–474, 1989.

    Google Scholar 

  55. Chan HSL, Thorner PS, Haddad G, Gaullie BL: The multidrug-resistant phenotype in retinoblastoma correlates with P-glycoprotein expression. Ophthalmology 98:1425–1431, 1991.

    Google Scholar 

  56. Grier HE, Weinstein HJ: Chapter 20. Acute myelogenous leukemia. In: Pizzo PA, Poplack DG (eds) Principles and Practice of Pediatric Oncology. J. B. Lippincott Company, Philadelphia, 1993, pp 483–500.

    Google Scholar 

  57. Poplack DG: Chapter 19. Acute lymphoblastic leukemia. In: Pizzo PA, Poplack DG (eds) Principles and Practice of Pediatric Oncology. J. B. Lippincott Company, Philadelphia, 1993, pp 431–481.

    Google Scholar 

  58. Ubezio P, Limonta M, D'Incalci G, Damia G, Masera G, Giudici JS, Wolverton JS, Beck WT: Failure to detect the P-glycoprotein multidrug resistant phenotype in cases of resistant childhood acute lymphocytic leukaemia. Eur J Cancer Clin Oncol 25:1895–1899, 1989.

    Google Scholar 

  59. Rothenberg ML, Mickley LA, Cole DE, Balis FM, Tsuruo T, Poplack DG, Fojo AT: Expression of the mdr1/P-170 gene in patients with acute lymphoblastic leukemia. Blood 74:1388–1395, 1989.

    Google Scholar 

  60. Ivy SP, Smith JK, Speciale A, Sather H, Hammond GD, Raman GH: Detection of mdr1 gene expression using polymerase chain reaction (PCR) in childhood acute lymphoblastic leukemia (ALL) at diagnosis. Proc Amer Assoc Cancer Res 33:473, 1992 (abstract).

    Google Scholar 

  61. Gillan E, Knoppel E, Feusner J, Wells R, Cairo MS: Increased detection of multiple drug resistance expression of pediatric leukemias at diagnosis and relapse by reverse transcriptase polymerase chain reaction. Proc Am Assoc Cancer Res 33:261, 1992 (abstract).

    Google Scholar 

  62. Goasguen JE, Dossot J, Fardel O, Mee FL, Gall EL, Leblay R, Leprise PY, Chaperon J, Fauchet R: Expression of the multidrug resistance-associated P-Glycoprotein (P-170) in 59 cases of de novo acute lymphoblastic leukemia: Prognostic implications. Blood 81:2394–2398, 1993.

    Google Scholar 

  63. Pieters R, Hongo T, Loonen AH, Huismans DR, Broxterman HJ, Hahlen K: Different types of non-P-glycoprotein mediated multiple drug resistance in children with relapsed acute lymphoblastic leukaemia. Br J Cancer 65:691–697, 1992.

    Google Scholar 

  64. Brophy NA, Marie JP, Rojas VA, Warnke RA, McFall PJ, Smith SD, Sikic BI: Mdr1 gene expression in childhood acute lymphoblastic leukemias and lymphomas: a critical evaluation by four techniques. Leukemia 8:327–335, 1994.

    Google Scholar 

  65. Ford JM: Modulators of multidrug resistance. Hematol Oncol Clin NA 9:337–361, 1995.

    Google Scholar 

  66. Bessho F, Kinumaki H, Kobayashi M, Habu H, Nakamura K, Yokota S, Tsuruo T, Kobayashi N: Treatment of children with refractory acute lymphocytic leukemia with vincristine and diltiazem. Med Pediatr Oncol 15:199–202, 1985.

    Google Scholar 

  67. Cairo MS, Siegel S, Anas N, Sender L: Clinical trials of continuous infusion verapamil, bolus vinblastine, and continuous infusion VP-16 in drug-resistant pediatric tumors. Cancer Res 49:1063–1066, 1989.

    Google Scholar 

  68. List AF, Spier C, Greer J, Wolff S, Hutter J, Dorr R, Salmon SE, Futscher B, Baier M, Dalton W: Phase I/II trial of cyclosporine as a chemotherapy-resistance modifier in acute leukemia. J Clin Oncol 11:1652–1660, 1993.

    Google Scholar 

  69. Chan HSL, Thorner PS, Weitzman S, Solh H, Koren G, Thiessen J, Haddad G, Giesbrecht E, Verjee Z, Greenberg ML, Gallie BL, Long V: Cyclosporine A for reversal of multidrug resistance in childhood malignancies. Proc Am Assoc Cancer Res 32:478, 1992 (abstract).

    Google Scholar 

  70. Chan HSL, DeBoer G, Koren G, Ling V, Gallie BL: Cyclosporin A-modulated chemotherapy with focal therapy: a new approach to retinoblastoma. Proc Am Assoc Cancer Res 35:359, 1994 (abstract).

    Google Scholar 

  71. Schwartz CL, Hicks D, Weiner M, Rosier R: The use of CSAV to overcome drug resistance. Proc Am Soc Clin Oncol 12:1993 (abstract).

  72. Theis JGW, Liau-Chu M, Chan HSL, Doyle J, Greenberg ML, Koren G: Anaphylactoid reactions in children receiving high-dose intravenous cyclosporine for reversal of tumor resistance: the causative role of improper dissolution of cremphor EL. J Clin Oncol 13:2508–2516, 1995.

    Google Scholar 

  73. Tsuruo T, Iida H, Naganuma K, Tsukagoshi S, Sakurai Y: Promotion by verapamil of vincristine responsiveness in tumor cell lines intrinsically resistant to the drug. Cancer Res 43:808–813, 1983.

    Google Scholar 

  74. Tsuruo T, Iida H, Nojiri M, Tsukagoshi S, Sakurai Y: Circumvention of vincristine and adriamycin resistance in vitro and in vivo by calcium influx blockers. Cancer Res 48:2905–2910, 1983.

    Google Scholar 

  75. Fisher GA, Sikic BI: Clinical studies with modulators of multidrug resistance. Hematol Oncol Clin NA 9:363, 1995.

    Google Scholar 

  76. Slater LM, Sweet P, Stupecky M, Gupta S: Cyclosporin A reverses vincristine and daunorubicin resistance in acute lymphatic leukemia in vitro. J Clin Invest 77:1405–1408, 1986.

    Google Scholar 

  77. Boesch D, Muller K, Pourtier-Manzanedo A, Loor F: Restoration of daunomycin retention in multidrug-resistant P388 cells by submicromolar concentrations of SDZ PSC-833, a non-immunosuppresive cyclosporin derivative. Ex Cell Res 196:26–32, 1991.

    Google Scholar 

  78. Dahl G, Brophy N, Grier H, Weinstein H, Sikic B, Arceci R: Mitoxantrone, etoposide and cyclosporine A (MEC) therapy for relapsed and refractory acute myelogenous leukemia (AML). A Pediatric Oncology Group (POG) phase II trial. Ann Hematol 68:A32, 1994 (abstract).

    Google Scholar 

  79. Dahl G, Dunussi K, Mogul M, Brophy N, Lowe K, Grier H, Sikic B, Weinstein H, Arceci R: A Pediatric Oncology Group (POG) phase II trial of mitoxantrone, etoposide and cyclosporine A (MEC) therapy for relapsed or refractory acute myelogenous leukemia (AML). Proc Amer Assoc Cancer Res 35:332, 1994 (abstract).

    Google Scholar 

  80. Lum BL, Kaubisch S, Yahanda AM, Adler KM, Jew L, Ehsan MN, Brophy NA, Halsey M, Gosland MP, Sikic BI: Alteration of etoposide pharmacokinetics and pharmacodynamics by cyclosporine in a phase I trial to modulate multidrug resistance. J Clin Oncol 10(10):1635–1642, 1992.

    Google Scholar 

  81. Cole SP, Sparks KE, Fraser K, Loe DW, Grant CE, Wilson GM, Deeley RG: Pharmacological characterization of multidrug resistant MRP-transfected human tumor cells. Cancer Res 54:5902–5910, 1994.

    Google Scholar 

  82. Muller M, Meijer C, Zaman GJ, Borst P, Scheper RJ, Mulder NH, de Vries EG, Jansen PL: Overexpression of the gene encoding the multidrug resistance-associated protein results in increased ATP-dependent glutathione S-conjugate transport. Proc Natl Acad Sci USA 91:13033–13037, 1994.

    Google Scholar 

  83. Bordow SB, Haber M, Madafiglio J, Cheung B, Marshall GM, Norris MD: Expression of the multidrug resistance-associated protein (MRP) gene correlates with amplification and overexpression of the N-myc oncogene in childhood neuroblastoma. Cancer Res 54:5036–5040, 1994.

    Google Scholar 

  84. Norris MD, Bordow SB, Marshall GM, Haber PS, Conn SL, Haber M: Expression of the gene for multidrug-resistance-associated protein and outcome in patients with neuroblastoma. N Engl J Med 334:231–238, 1996.

    Google Scholar 

  85. Lowe SW, Ruley HE, Jacks T, Houseman DE: p53-Dependent apoptosis modulates the cytotoxicity of anti-cancer agents. Cell 74:957–967, 1993.

    Google Scholar 

  86. Reed JC: BCL-2: Prevention of apoptosis as a mechanism of drug resistance. Hematol Oncol Clin NA 9:451–473, 1995.

    Google Scholar 

  87. Bloch CA, Castle VP: Bcl-2 inhibits chemotherapy-induced apoptosis in neuroblastoma. Cancer Res 54:3253–3259, 1994.

    Google Scholar 

  88. Nooter K, Boersma AW, Oostru RG, Burger H: Constitutive expression of the c-H-ras oncogene inhibits doxorubicin-induced apoptosis and promotes cell survival in a rhabdomyosarcoma cell line. Br J Can 71:556–561, 1995.

    Google Scholar 

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  1. Division of Pediatrics, The University of Texas M.D., Anderson Cancer Center, 1515 Holcombe Blvd., 77030, Houston, TX, USA

    John F. Kuttesch Jr.

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Address for offprints: John F. Kuttesch, Jr., Division of Pediatrics, The University of Texas M.D., Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA

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Kuttesch, J.F. Multidrug resistance in pediatric oncology. Invest New Drugs 14, 55–67 (1996). https://doi.org/10.1007/BF00173683

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