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Cross-Resistance Studies of Isogenic Drug-Resistant Breast Tumor Cell Lines Support Recent Clinical Evidence Suggesting that Sensitivity to Paclitaxel may be Strongly Compromised by Prior Doxorubicin Exposure

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Abstract

Less than half of breast cancer patients respond to second-line chemotherapy with paclitaxel after failing treatment with anthracyclines such as doxorubicin. A recent clinical trial by Paridaens et al. [J. Clin. Oncol. 18: 724–733, 2000] examined whether patients may derive a better clinical benefit if paclitaxel was administered before doxorubicin. While overall survival was similar regardless of the order of drug administration, a >4-fold reduction in the response rate to paclitaxel was observed after late crossover from doxorubicin, compared to the response rate to doxorubicin after late crossover from paclitaxel. This may be related to differences in the ability of the drugs to induce cross-resistance to each other. To test this hypothesis, we examined whether isogenic breast tumor cells selected for resistance to doxorubicin exhibit greater cross-resistance to paclitaxel and other drugs than identical cells selected for resistance to paclitaxel. We found that cells selected for resistance to paclitaxel showed strong resistance (≥40-fold) to paclitaxel and docetaxel, with little cross-resistance (4-fold) to doxorubicin. In contrast, cells selected for resistance to doxorubicin exhibited 50-fold resistance to doxorubicin and a dramatic 4700-fold and 14,600-fold cross-resistance to paclitaxel and docetaxel, respectively. Doxorubicin-resistant cells exhibited higher P-glycoprotein and breast cancer resistance protein (BCRP) levels than paclitaxel-resistant cells. In addition, procaspase-9 was strongly downregulated in doxorubicin-resistant cells but not in paclitaxel-resistant cells. These differences may account for the contrasting cross-resistance profiles observed for the two cell lines and may help to explain why treatment of breast cancer patients with paclitaxel appears to be compromized by prior doxorubicin exposure.

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References

  1. Zijlstra JG, de Jong S, de Vries EG, Mulder NH: Topoisomerases, new targets in cancer chemotherapy. Med Oncol Tumor Pharmacother 7: 11–18, 1990

    Google Scholar 

  2. Nielsen D, Jensen JB, Dombernowsky P: Epirubicin cardiotoxicity: a study of 135 patients with advanced breast cancer. J Clin Oncol 8: 1806–1810, 1990

    Google Scholar 

  3. Richardson DS, Johnson SA: Anthracyclines in haematology: preclinical studies, toxicity and delivery systems. Blood Rev 11: 201–223, 1997

    Google Scholar 

  4. Capranico G, Tinelli S, Zunino F: Formation, resealing and persistence of DNA breaks produced by 4-demethoxydaunorubicin in P388 leukemia cells. Chem Biol Interact 72: 113–123, 1989

    Google Scholar 

  5. Wu XX, Mizutani Y, Kakehi Y, Yoshida O, Ogawa O: Enhancement of Fas-mediated apoptosis in renal cell cacinoma cells by adriamycin. Cancer Res 60: 2912–2918, 2000

    Google Scholar 

  6. Yamaoka M, Yamaguchi S, Suzuki T, Okuyama M, Nitobe J, Nakamura N, Mitsui Y, Tomoike H: Apoptosis in rat cardiac myocytes induced by Fas ligand: priming for Fas-mediated apoptosis with doxorubicin. J Mol Cell Cardiol 32: 881–889, 2000

    Google Scholar 

  7. Chazard M, Pellae-Cosset B, Garet F, Soares JA, Lucidi B, Lavail Y, Lenaz L: [Taxol (paclitaxel), first molecule of a new class of cytotoxic agents: taxanes]. Bull Cancer 81: 173–181, 1994

    Google Scholar 

  8. Arioka H, Saijo N: [Microtubules and antineoplastic drugs]. Gan To Kagaku Ryoho 21: 83–590, 1994

    Google Scholar 

  9. Distefano M, Scambia G, Ferlini C, Gaggini C, De Vincenzo R, Riva A, Bombardelli E, Ojima I, Fattorossi A, Panici PB, Mancuso S: Anti-proliferative activity of a new class of taxanes (14beta-hydroxy-10-deacetylbaccatin III derivatives) on multidrug-resistance-positive human cancer cells. Int J Cancer 72: 844–850, 1997

    Google Scholar 

  10. Moos PJ, Fitzpatrick FA: Taxane-mediated gene induction is independent of microtubule stabilization: induction of transcription regulators and enzymes that modulate inflammation and apoptosis. Proc Natl Acad Sci USA 95: 3896–3901, 1998

    Google Scholar 

  11. Citron M, Berry D, Cirrincione C, Hudis C, Winer E, Gradishar W, Davidson N, Martino S, Livingston R, Ingle J, Perez E, Carpenter J, Hurd D, Holland J, Smith B, Sartor C, Leung E, Abrams J, Schilsl R, Muss H, Norton L: Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 8: 1431–1439, 2003

    Google Scholar 

  12. Berg CD, Swain SM: Results of concomitantly administered chemoradiation for locally advanced noninflammatory breast cancer. Semin Radiat Oncol 4: 226–235, 1994

    Google Scholar 

  13. Ueno NT, Buzdar AU, Singletary SE, Ames FC, McNeese MD, Holmes FA, Theriault RL, Strom EA, Wasaff BJ, Asmar L, Frye D, Hortobagyi GN: Combined-modality treatment of inflammatory breast carcinoma: twenty years of experience at M. D. Anderson Cancer Center. Cancer Chemother Pharmacol 40: 321–329, 1997

    Google Scholar 

  14. Crown J: Nonanthracycline containing docetaxel-based combinations in metastatic breast cancer. Oncologistz 6(Suppl 3): 17–21, 2001

    Google Scholar 

  15. Juliano RL, Ling V: A surface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455: 152–162, 1976

    Google Scholar 

  16. Beck WT, Mueller TJ, Tanzer LR: Altered surface membrane glycoproteins in Vinca alkaloid-resistant human leukemic lymphoblasts. Cancer Res 39: 2070–2076, 1979

    Google Scholar 

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

    Google Scholar 

  18. Fry AM, Chresta CM, Davies SM, Walker MC, Harris AL, Hartley JA, Masters JR, Hickson ID: Relationship between topoisomerase II level and chemosensitivity in human tumor cell lines. Cancer Res 51: 6592–6595, 1991

    Google Scholar 

  19. Giaccone G, Gazdar AF, Beck H, Zunino F, Capranico G: Multidrug sensitivity phenotype of human lung cancer cells associated with topoisomerase II expression. Cancer Res 52: 1666–1674, 1992

    Google Scholar 

  20. Balcer-Kubiczek EK, Yin J, Lin K, Harrison GH, Abraham JM, Meltzer SJ: p53 mutational status and survival of human breast cancer MCF-7 cell variants after exposure to X rays or fission neutrons. Radiat Res 142: 256–262, 1995

    Google Scholar 

  21. Aas T, Borresen AL, Geisler S, Smith-Sorensen B, Johnsen H, Varhaug JE, Akslen LA, Lonning PE: Specific P53 mutations are associated with de novo resistance to doxorubicin in breast cancer patients. Nat Med 2: 811–814, 1996

    Google Scholar 

  22. Cai Z, Stancou R, Korner M, Chouaib S: Impairment of Fas-antigen expression in adriamycin-resistant but not TNFresistant MCF-7 tumor cells. Int J Cancer 68: 535–546, 1996

    Google Scholar 

  23. Batist G, Tulpule A, Sinha BK, Katki AG, Myers CE, Cowan KH: Overexpression of a novel anionic glutathione transferase in multidrug-resistant human breast cancer cells. J Biol Chem 261: 15544–15549, 1986

    Google Scholar 

  24. Batist G, Behrens BC, Makuch R, Hamilton TC, Katki AG, Louie KG, Myers CE, Ozols RF: Serial determinations of glutathione levels and glutathione-related enzyme activities in human tumor cells in vitro. Biochem Pharmacol 35: 2257–2259, 1986

    Google Scholar 

  25. Harris AL, Hochhauser D: Mechanisms of multidrug resistance in cancer treatment. Acta Oncol 31: 205–213, 1992

    Google Scholar 

  26. Horwitz SB, Cohen D, Rao S, Ringel I, Shen HJ, Yang CP: Taxol: mechanisms of action and resistance. In: Proceedings of the Second National Cancer Institute Workshop on Taxol an Taxus, J Natl Cancer Inst Monogr 15, Washington US Dept of Health and Human Services, 1993, pp 55–61

    Google Scholar 

  27. Cabral F, Abraham I, Gottesman MM: Isolation of a taxolresistant Chinese hamster ovary cell mutant that has an alteration in alpha-tubulin. Proc Natl Acad Sci USA 78: 4388–4391, 1981

    Google Scholar 

  28. Schibler MJ, Huang B: The colR4 and colR15 beta-tubulin mutations in Chlamydomonas reinhardtii confer altered sensitivities to microtubule inhibitors and herbicides by enhancing microtubule stability. J Cell Biol 113: 605–614, 1991

    Google Scholar 

  29. Anand S, Penrhyn-Lowe S, Venkitaraman A: AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell 3: 51–62, 2003

    Google Scholar 

  30. Wahl A, Donaldson K, Fairchild C, Lee F, Foster S, Demer G, Galloway D: Loss of normal p53 function confers sensitization to Taxol by increasing G2/M arrest and apoptosis. Nat Med 2: 72–79, 1996

    Google Scholar 

  31. Basu A, Haldar S: Identification of a novel Bcl-xL phosphorylation site regulation the sensitivity of taxol-or 2-methoxyestradiol-induced apoptosis. FEBS Lett 538: 41–47, 2003

    Google Scholar 

  32. Ferlini C, Raspaglio G, Mozzetti S, Distefano M, Filippetti F, Martinelli Ferrandina G, Gallo D, Ranelletti F, Scambia G: Bcl-2 down-regulation is a novel mechanism of paclitaxel resistance. Mol Pharmacol 64: 51–58, 2003

    Google Scholar 

  33. Clark A, West K, Streicher S, Dennis P: Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol Cancer Ther 1: 707–717, 2002

    Google Scholar 

  34. Seidman AD, Norton L, Reichman BS, Crown JP, Yao TJ, Heelan R, Hakes TB, Lebwohl DE, Gilewski TA, Surbone A: Preliminary experience with paclitaxel (Taxol) plus recombinant human granulocyte colony-stimulating factor in the treatment of breast cancer. Semin Oncol 20: 40–45, 1993

    Google Scholar 

  35. Reichman BS, Seidman AD, Crown JP, Heelan R, Hakes TB, Lebwohl DE, Gilewski TA, Surbone A, Currie V, Hudis CA: Paclitaxel and recombinant human granulocyte colonystimulating factor as initial chemotherapy for metastatic breast cancer. J Clin Oncol 11: 1943–1951, 1993

    Google Scholar 

  36. Paridaens R, Biganzoli L, Bruning P, Klijn JG, Gamucci T, Houston S, Coleman R, Schachter J, van Vreckem A, Sylvester R, Awada A, Wildiers J, Piccart M: Paclitaxel versus doxorubicin as first-line single-agent chemotherapy for metastatic breast cancer: a European Organization for Research and Treatment of Cancer Randomized Study with cross-over. J Clin Oncol 18: 724–733, 2000

    Google Scholar 

  37. Chadderton A, Villeneuve DJ, Gluck S, Kirwan-Rhude AF, Gannon BR, Blais DE, Parissenti AM: Role of specific apoptotic pathways in the restoration of paclitaxel-induced apoptosis by valspodar in doxorubicin-resistant MCF-7 breast cancer cells. Breast Cancer Res Treat 59: 231–244, 2000

    Google Scholar 

  38. Elias, Jules M: Immunohistopathology: A Practical Approach to Diagnosis. Vol. 357 American Society of Clinical Pathology Press, Chicago, USA, 1990

    Google Scholar 

  39. Shain KH, Dalton, WS: Cell adhesion is a key determinant in de novo multidrug resistance (MDR): new targets for the prevention of acquired MDR. Mol Cancer Ther 1: 69–78, 2001

    Google Scholar 

  40. Dalton WS, Durie BG, Alberts DS, Gerlach JH, Cress AE: Characterization of a new drug-resistant human myeloma cell line that expresses P-glycoprotein. Cancer Res 46: 5125–5130, 1986

    Google Scholar 

  41. Bhalla K, Huang Y, Tang C, Self S, Ray S, Mahoney ME, Ponnathpur V, Tourkina E, Ibrado AM, Bullock G: Characterization of a human myeloid leukemia cell line highly resistant to taxol. Leukemia 8: 465–475, 1994

    Google Scholar 

  42. Li D, Jang S, Kim J, Wientjes M, Au J: Enhanced druginduced apoptosis associated with P-glycoprotein overexpression is specific to antimicrotubule agents. Pharm Res 20: 45–50, 2003

    Google Scholar 

  43. 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 

  44. Boesch D, Gaveriaux C, Jachez B, Pourtier-Manzanedo A, Bollinger P, Loor F: In vivo circumvention of P-glycoproteinmediated multidrug resistance of tumor cells with SDZ PSC 833. Cancer Res 51: 4226–4233, 1991

    Google Scholar 

  45. Jachez B, Nordmann R, Loor F: Restoration of taxol sensitivity of multidrug-resistant cells by the cyclosporine SDZ PSC 833 and the cyclopeptolide SDZ 280-446. J Natl Cancer Inst 85: 478–483, 1993

    Google Scholar 

  46. Jette L, Murphy GF, Beliveau R: Drug binding to Pglycoprotein is inhibited in normal tissues following SDZPSC 833 treatment. Int J Cancer 76: 729–737, 1998

    Google Scholar 

  47. Cabot MC, Giuliano AE, Han TY, Liu YY: SDZ PSC 833, the cyclosporine A analogue and multidrug resistance modulator, activates ceramide synthesis and increases vinblastine sensitivity in drug-sensitive and drug-resistant cancer cells. Cancer Res 59: 880–885, 1999

    Google Scholar 

  48. Lage H, Dietel M: Effect of the breast-cancer resistance protein on atypical multidrug resistance. Lancet Oncol 1: 169–175, 2000

    Google Scholar 

  49. Litman T, Brangi M, Hudson E, Fetsch P, Abati A, Ross D, Miyake K, Resau J, Bates S: The multidrug-resistant phenotype associated with overexpression of the new ABC half-transporter, MXR (ABCG2). J Cell Sci 113: 2011–2021, 2000

    Google Scholar 

  50. Robey R, Medina-Perez W, Nishiyama K, Lahusen T, Miyake K, Litman T, Senderowicz A, Ross D, Bates S: Overexpression of the ATP-binding cassette half-transporter, ABCG2 (Mxr/BCrp/ABCP1), in flavopiridol-resistant human breast cancer cells. Clin Cancer Res 7: 145–152, 2001

    Google Scholar 

  51. Rabindran S, Ross D, Doyle L, Yang W, Greenberger L: Fumitremorgin C reverses multidrug resistance in cells transfected with the breast cancer resistance protein. Cancer Res 60: 47–50, 2000

    Google Scholar 

  52. Doyle LA, Yang W, Abruzzo LV, Krogmann T, Gao Y, Rishi AK, Ross DD: A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci USA 95: 15665–15670, 1998

    Google Scholar 

  53. Jazirehi AR, Ng CP, Gan XH, Schiller G, Bonavida B: Adriamycin sensitizes the adriamycin-resistant 8226/Dox40 human multiple myeloma cells to Apo2L/tumor necrosis factor-related apoptosis-inducing ligand-mediated (TRAIL) apoptosis. Clin Cancer Res 7: 3874–3883, 2001

    Google Scholar 

  54. Marks DC, Su GM, Davey RA, Davey MW: Extended multidrug resistance in haemopoietic cells. Br J Haematol 95: 587–595, 1996

    Google Scholar 

  55. Gosland MP, Gillespie MN, Tsuboi CP, Tofiq S, Olson JW, Crooks PA, Aziz SM: Reversal of doxorubicin, etoposide, vinblastine, and taxol resistance in multidrug resistant human sarcoma cells by a polymer of spermine. Cancer Chemother Pharmacol 37: 593–600, 1996

    Google Scholar 

  56. Dumontet C, Duran GE, Steger KA, Beketic-Oreskovic L, Sikic BI: Resistance mechanisms in human sarcoma mutants derived by single-step exposure to paclitaxel (Taxol). Cancer Res 56: 1091–1097, 1996

    Google Scholar 

  57. Ark-Otte J, Samelis G, Rubio G, Lopez Saez JB, Pinedo HM, Giaccone G: Effects of tubulin-inhibiting agents in human lung and breast cancer cell lines with different multidrug resistance phenotypes. Oncol Rep 5: 249–255, 1998

    Google Scholar 

  58. Duan Z, Feller AJ, Penson RT, Chabner BA, Seiden MV: Discovery of differentially expressed genes associated with paclitaxel resistance using cDNA array technology: analysis of interleukin (IL) 6, IL-8, and monocyte chemotactic protein 1 in the paclitaxel-resistant phenotype. Clin Cancer Res 5: 3445–3453, 1999

    Google Scholar 

  59. Ikubo S, Takigawa N, Ueoka H, Kiura K, Tabata M, Shibayama T, Chikamori M, Aoe K, Matsushita A, Harada M: In vitro evaluation of antimicrotubule agents in human smallcell lung cancer cell lines. Anticancer Res 19: 3985–3988, 1999

    Google Scholar 

  60. NicAmhlaoibh R, Heenan M, Cleary I, Touhey S, O'Loughlin C, Daly C, Nunez G, Scanlon KJ, Clynes M: Altered expression of mRNAs for apoptosis-modulating proteins in a low level multidrug resistant variant of a human lung carcinoma cell line that also expresses mdr1 mRNA. Int J Cancer 82: 368–376, 1999

    Google Scholar 

  61. Burns BS, Edin ML, Lester GE, Tuttle HG, Wall ME, Wani MC, Bos GD: Selective drug resistant human osteosarcoma cell lines. Clin Orthop 259–267, 2001

  62. Zhou J, Cheng SC, Luo D, Xie Y: Study of multi-drug resistant mechanisms in a taxol-resistant hepatocellular carcinoma QGY-TR 50 cell line. Biochem Biophys Res Commun 280: 1237–1242, 2001

    Google Scholar 

  63. Combates NJ, Rzepka RW, Chen YN, Cohen D: NF-IL6, a member of the C/EBP family of transcription factors, binds and trans-activates the human MDR1 gene promoter. J Biol Chem 269: 29715–29719, 1994

    Google Scholar 

  64. Devarajan E, Chen J, Multani AS, Pathak S, Sahin AA, Mehta K: Human breast cancer MCF-7 cell line contains inherently drug-resistant subclones with distinct genotypic and phenotypic features. Int J Oncol 20: 913–920, 2002

    Google Scholar 

  65. Batist G, Tulpule A, Sinha BK, Katki AG, Myers CE, Cowan KH: Overexpression of a novel anionic glutathione transferase in multidrug-resistant human breast cancer cells. J Biol Chem 261: 15544–15549, 1986

    Google Scholar 

  66. Scudiero DA, Monks A, Sausville EA: Cell line designation change: multidrug-resistant cell line in the NCI anticancer screen [letter]. J Natl Cancer Inst 90: 862, 1998

    Google Scholar 

  67. Broxterman H, Lankelma J, Pinedo H, Eekman C, Wahrer D, Ossenkoppele G, Schuurhuis G: Theoretical and practical considerations for the measurement of P-glycoprotein function in acute myeloid leukemia. Leukemia 11: 1110–1118, 1997

    Google Scholar 

  68. Cabot MC, Han TY, Giuliano AE: The multidrug resistance modulator SDZ PSC 833 is a potent activator of cellular ceramide formation. FEBS Lett 431: 185–188, 1998

    Google Scholar 

  69. Bezombes C, Maestre N, Laurent G, Levade T, Bettaieb A, Jaffrezou JP: Restoration of TNF-alpha-induced ceramide generation and apoptosis in resistant human leukemia KG1a cells by the P-glycoprotein blocker PSC833. FASEB J 12: 101–109, 1998

    Google Scholar 

  70. Allen JD, Brinkhuis RF, Wijnholds J, Schinkel AH: The mouse Bcrp1/Mxr/Abcp gene: amplification and overexpression in cell lines selected for resistance to topotecan, mitoxantrone, or doxorubicin. Cancer Res 59: 4237–4241, 1999

    Google Scholar 

  71. Kanzaki A, Toi M, Nakayama K, Bando H, Mutoh M, Uchida T, Fukumoto M, Takebayashi Y: Expression of multidrug resistance-related transporters in human breast carcinoma. Jpn J Cancer Res 92: 452–458, 2001

    Google Scholar 

  72. Borst P, Schinkel AH: Genetic dissection of the function of mammalian P-glycoproteins. Trends Genet 13: 217–222, 1997

    Google Scholar 

  73. Wu GS, Ding Z: Caspase 9 is required for p53-dependent apoptosis and chemosensitivity in a human ovarian cancer cell line. Oncogene 21: 1–8, 2002

    Google Scholar 

  74. Perkins CL, Fang G, Kim CN, Bhalla KN: The role of Apaf-1, caspase-9, and bid proteins in etoposide-or paclitaxel-induced mitochondrial events during apoptosis. Cancer Res 60: 1645–1653, 2000

    Google Scholar 

  75. Kornblau SM, Estey E, Madden T, Tran HT, Zhao S, Consoli U, Snell V, Sanchez-Williams G, Kantarjian H, Keating M, Newman RA, Andreeff M: Phase I study of mitoxantrone plus etoposide with multidrug blockade by SDZ PSC-833 in relapsed or refractory acute myelogenous leukemia. J Clin Oncol 15: 1796–1802, 1997

    Google Scholar 

  76. Advani R, Saba HI, Tallman MS, Rowe JM, Wiernik PH, Ramek J, Dugan K, Lum B, Villena J, Davis E, Paietta E, Litchman M, Sikic BI, Greenberg PL: Treatment of refractory and relapsed acute myelogenous leukemia with combination chemotherapy plus the multidrug resistance modulator PSC 833 (Valspodar). Blood 93: 787–795, 1999

    Google Scholar 

  77. Villeneuve DJ, Hembruff SL, Kirwan AF, Parissenti AM: cDNA microarray analysis of isogenic paclitaxel-and doxorubicin-resistant breast tumor cell lines reveals drugspecific changes in gene expression accompanying the establishment of drug resistance, 2004 (in preparation)

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Authors and Affiliations

  1. Tumor Biology Research Program, Northeastern Ontario Regional Cancer Centre, Sudbury, Ont., Canada

    Baoqing Guo, David J. Villeneuve, Angie F. Kirwan & Amadeo M. Parissenti

  2. Department of Biology, Sudbury, Ont., Canada

    Stacey L. Hembruff & Amadeo M. Parissenti

  3. Department of Chemistry and Biochemistry, Laurentian University, Sudbury, Ont., Canada

    David E. Blais & Amadeo M. Parissenti

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  1. Baoqing Guo
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  2. David J. Villeneuve
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Guo, B., Villeneuve, D.J., Hembruff, S.L. et al. Cross-Resistance Studies of Isogenic Drug-Resistant Breast Tumor Cell Lines Support Recent Clinical Evidence Suggesting that Sensitivity to Paclitaxel may be Strongly Compromised by Prior Doxorubicin Exposure. Breast Cancer Res Treat 85, 31–51 (2004). https://doi.org/10.1023/B:BREA.0000021046.29834.12

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