Breast Cancer

, Volume 18, Issue 2, pp 103–119 | Cite as

The microtubule as a breast cancer target

Review Article
First Online:
Received:
Accepted:

Abstract

Manifestations of non-equilibrium polarity, random transgressions, and catastrophes are not conditions usually associated with a sense of normalcy. Yet these disquieting features distinguish a utilitarian behavior known as dynamic instability, the signature characteristic of the microtubule. Long known to be a tumor target, disruption of this fragile attribute is associated with some of the most effective agents used to treat breast cancer today. Although the biology of the microtubule is under intense investigation much still remains unknown. As such, our understanding of regulatory molecules and resistance mechanisms are still rudimentary, further compromising our ability to develop novel therapeutic strategies to improve microtubule inhibitors. This review focuses on several classes of anti-microtubule agents and their effects on the functional dynamics of the targeted polymer. The primary objective is to critically examine the molecular mechanisms that contribute to tumor cell death, tumor-resistance, and incident neurotoxicity.

Keywords

α-Tubulin β-Tubulin Dynamic instability Microtubule 
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References

  1. 1.
    Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.PubMedGoogle Scholar
  2. 2.
    Surveillance Epidemiology and End Results. SEER stat fact sheets: breast cancer. SEER Cancer Statistics Review 1975–2005. http://seer.concer.gov/statfacts/html/breast.html. Accessed 7 Apr 2010.
  3. 3.
    Nogales E, Wolf SG, Downing KH. Structure of the αβ tubulin dimer by electron crystallography. Nature. 1998;391:199–202.PubMedGoogle Scholar
  4. 4.
    Rassow J, von Ahsen O, Bömer U, Pfanner N. Molecular chaperones: towards a characterization of the heat-shock protein 70 family. Trends Cell Biol. 1997;7:129–33.Google Scholar
  5. 5.
    Hirata D, Masuda H, Eddison M, Toda T. Essential role of tubulin-folding cofactor D in microtubule assembly and its association with microtubules in fission yeast. EMBO J. 1998;17:667–76.Google Scholar
  6. 6.
    Nogales E, Whittaker M, Milligan RA, Downing KH. High-resolution model of the microtubule. Cell. 1999;96:79–88.PubMedGoogle Scholar
  7. 7.
    Desai A, Mitchison TJ. Microtubule polymerization dynamics. Annu Rev Cell Dev Biol. 1997;13:83–117.PubMedGoogle Scholar
  8. 8.
    Walker RA, Inoue S, Salmon ED. Asymmetric behavior of severed microtubule ends after ultraviolet-microbeam irradiation of individual microtubules in vitro. J Cell Biol. 1989;108:931–7.PubMedGoogle Scholar
  9. 9.
    Nogales E. Structural insights into microtubule function. Annu Rev Biochem. 2000;69:277–302.PubMedGoogle Scholar
  10. 10.
    Dhamodharan R, Jordan MA, Thrower D, Wilson L, Wadsworth P. Vinblastine suppresses dynamics of individual microtubules in living interphase cells. Mol Biol Cell. 1995;6:1215–29.PubMedGoogle Scholar
  11. 11.
    Singer WD, Jordan MA, Wilson L, Himes RH. Binding of vinblastine to stabilized microtubules. Mol Pharmacol. 1989;36:366–70.PubMedGoogle Scholar
  12. 12.
    Rai SS, Wolff J. Localization of the vinblastine binding site on β-tubulin. J Biol Chem. 1996;271:14707–11.PubMedGoogle Scholar
  13. 13.
    Rao S, Krauss NE, Heerding JM, Swindell CS, Ringel I, Orr GA, et al. 3′-(p-azidobenzamido)taxol photolabels the N-terminal 31 amino acids of beta-tubulin. J Biol Chem. 1994;269:3132–4.PubMedGoogle Scholar
  14. 14.
    Romero A, Rabinovich MG, Vallejo CT, Perez JE, Rodriguez R, Cuevas MA, et al. Vinorelbine as first-line chemotherapy for metastatic breast carcinoma. J Clin Oncol. 1994;12:336–41.PubMedGoogle Scholar
  15. 15.
    Twelves CJ, Dobbs NA, Curnow A, Coleman RE, Stewart AL, Tyrrell CJ, et al. A phase II multicentre, UK study of vinorelbine in advanced breast cancer. Br J Cancer. 1994;70:990–3.PubMedGoogle Scholar
  16. 16.
    García-Conde J, Lluch A, Martin M, Casado A, Gervasio H, De Oliveira C, et al. Phase II trial of weekly i.v. vinorelbine in first-line advanced breast cancer chemotherapy. Ann Oncol. 1994;5:854–7.PubMedGoogle Scholar
  17. 17.
    Woodard S, Nadella PC, Kotur L, Wilson J, Burak WE, Shapiro CL. Older women with breast carcinoma are less likely to receive adjuvant chemotherapy: evidence of possible age bias? Cancer. 2003;98:1141–9.PubMedGoogle Scholar
  18. 18.
    Vogel C, O’Rourke M, Winer E, Hochster H, Chang A, Adamkiewicz B, et al. Vinorelbine as first-line chemotherapy for advanced breast cancer in women 60 years of age or older. Ann Oncol. 1999;10:397–402.PubMedGoogle Scholar
  19. 19.
    Burstein HJ, Kuter I, Campos SM, Gelman RS, Tribou L, Parker LM, et al. Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer. J Clin Oncol. 2001;19:2722–30.PubMedGoogle Scholar
  20. 20.
    Pegram M, Hsu S, Lewis G, Pietras R, Beryt M, Sliwkowski M, et al. Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers. Oncogene. 1999;18:2241–51.PubMedGoogle Scholar
  21. 21.
    Sirotnak FM, Danenberg KD, Chen J, Fritz F, Danenberg PV. Markedly decreased binding of vincristine to tubulin in vinca alkaloid-resistant Chinese hamster cells is associated with selective overexpression of α and β isoforms. Biochem Biophys Res Commun. 2000;269:21–4.PubMedGoogle Scholar
  22. 22.
    Derry WB, Wilson L, Khan IA, Luduena RF, Jordan MA. Taxol differentially modulates the dynamics of microtubules assembled from unfractionated and purified beta-tubulin isotypes. Biochemistry. 1997;36:3554–62.PubMedGoogle Scholar
  23. 23.
    Ranganathan S, Dexter DW, Benetatos CA, Chapman AE, Tew KD, Hudes GR. Increase of beta(III)- and beta(IVa)-tubulin isotopes in human prostate carcinoma cells as a result of estramustine resistance. Cancer Res. 1996;56:2584–9.PubMedGoogle Scholar
  24. 24.
    Montgomery RB, Guzman J, O’Rourke DM, Stahl WL. Expression of oncogenic epidermal growth factor receptor family kinases induces paclitaxel resistance and alters beta-tubulin isotype expression. J Biol Chem. 2000;275:17358–63.PubMedGoogle Scholar
  25. 25.
    Zhang CC, Yang JM, White E, Murphy M, Levine A, Hait WN. The role of MAP4 expression in the sensitivity to paclitaxel and resistance to vinca alkaloids in p53 mutant cells. Oncogene. 1998;16:1617–24.PubMedGoogle Scholar
  26. 26.
    Chapin SJ, Lue CM, Yu MT, Bulinski JC. Differential expression of alternatively spliced forms of MAP4: a repertoire of structurally different microtubule-binding domains. Biochemistry. 1995;34:2289–301.PubMedGoogle Scholar
  27. 27.
    Shen Y, Shenk T. Relief of p53-mediated transcriptional repression by the adenovirus E1B 19-kDa protein or the cellular Bcl-2 protein. Proc Natl Acad Sci USA. 1994;91:8940–4.PubMedGoogle Scholar
  28. 28.
    Sabbatim P, McCormick F. Phosphoinositide 3-OH kinase (PI3K) and PKB/Akt delay the onset of p53-mediated, transcriptionally dependent apoptosis. J Biol Chem. 1999;274:24263–9.Google Scholar
  29. 29.
    Zhou BP, Liao Y, Xia W, Zou Y, Spohn B, Hung M-C. HER-2/neu induces p53 ubiquitination via Akt-mediated MDM2 phosphorylation. Nat Cell Biol. 2001;3:973–82.PubMedGoogle Scholar
  30. 30.
    Remillard S, Rebhun LI, Howie GA, Kupchan SM. Antimitotic activity of the potent tumor inhibitor maytansine. Science. 1975;189:1002–5.PubMedGoogle Scholar
  31. 31.
    Chari RV, Martell BA, Gross JL, Cook SB, Shah SA, Blättler WA, et al. Immunoconjugates containing novel maytansinoids: promising anticancer drugs. Cancer Res. 1992;52:127–31.PubMedGoogle Scholar
  32. 32.
    Bhattacharyya B, Wolff J. Maytansine binding to the vinblastine sites of tubulin. FEBS Lett. 1977;75:159–62.PubMedGoogle Scholar
  33. 33.
    Kupchan SM, Sneden AT, Branfman AR, Howie GA, Rebhun LI, McIvor WE, et al. Structural requirements for antileukemic activity among the naturally occurring and semisynthetic maytansinoids. J Med Chem. 1978;21:31–7.PubMedGoogle Scholar
  34. 34.
    Blum RH, Wittenberg BK, Canellos GP, Mayer RJ, Skarin AT, Henderson IC, et al. A therapeutic trial of maytansine. Cancer Clin Trials. 1978;1:113–7.PubMedGoogle Scholar
  35. 35.
    Eagan RT, Ingle JN, Rubin J, Frytak S, Moertel CG. Early clinical study of an intermittent schedule for maytansine (NSC-153858): brief communication. J Natl Cancer Inst. 1978;60:93–6.PubMedGoogle Scholar
  36. 36.
    Beeram M, Burris HA, Modi S, Birkner M, Girish S, Tibbitts J, et al. A phase I study of trastuzumab-DM1, a first-in-class HER2 antibody-drug conjugate (ADC), given every 3 weeks to patients with HER2+ metastatic breast cancer. J Clin Oncol. 2008;26:15S (Abstract 1028).Google Scholar
  37. 37.
    Vogel CL, Burris HA, Limentani S, Borson R, O’Shaughnessy J, Vukelja S, et al. A phase II study of trastuzumab-DM1 (T-DM1), a HER2 antibody-drug conjugate (ADC), in patients with HER2+ metastatic breast cancer (MBC): final results. J Clin Oncol. 2009;27:15s (Abstract 1017).Google Scholar
  38. 38.
    Krop I, LoRusso P, Miller KD, Modi S, Yardley D, Rodriguez G, et al. A phase II study of trastuzumab-DM1 (T-DM1), a novel HER2 antibody–drug conjugate, in patients with HER2+ metastatic breast cancer who were previously treated with an anthracycline, a taxane, capecitabine, lapatinib, and trastuzumab. Presented at San Antonio Breast Cancer Symposium (SABCS), San Antonio, TX, December 9–13, 2009 (Abstract 710).Google Scholar
  39. 39.
    Wang TH, Wang HS, Soong YK. Paclitaxel-induced cell death: where the cell cycle and apoptosis come together. Cancer. 2000;88:2619–28.PubMedGoogle Scholar
  40. 40.
    Donaldson KL, Goolsby G, Kiener PA, Wahl AF. Activation of p34cdc2 coincident with taxol-induced apoptosis. Cell Growth Differ. 1994;5:1041–50.PubMedGoogle Scholar
  41. 41.
    Shaulsky G, Goldfinger N, Tosky MS, Levine AJ, Rotter V. Nuclear localization is essential for the activity of p53 protein. Oncogene. 1991;6:2055–65.PubMedGoogle Scholar
  42. 42.
    Rowinsky EK, Donehower RC, Jones RJ, Tucker RW. Microtubule changes and cytotoxicity in leukemic cell lines treated with taxol. Cancer Res. 1988;48:4093–100.PubMedGoogle Scholar
  43. 43.
    Carmichael J, Degraff WG, Gazdar AF, Minna JD, Mitchell JB. Evaluation of a tetrazolium based semi-automated colorimetric assay: I. Assessment of chemosensitivity testing. Cancer Res. 1987;47:936–42.PubMedGoogle Scholar
  44. 44.
    Liebmann JE, Cook JA, Lipschultz C, Teague D, Fisher J, Mitchell JB. Cytotoxic studies of pacfitaxel (Taxol®) in human tumour cell lines. Br J Cancer. 1993;68:1104–9.PubMedGoogle Scholar
  45. 45.
    Liebmann JE, Cook JA, Lipschulz C, Teague D, Fisher J, Mitchell JB. The influence of Cremophor EL on the cell cycle effects of paclitaxel (Taxol) in human tumor cell lines. Cancer Chemother Pharmacol. 1994;33:331–9.PubMedGoogle Scholar
  46. 46.
    Dumontet C, Sikic BI. Mechanisms of action of and resistance to antitubulin agents: microtubule dynamics, drug transport, and cell death. J Clin Oncol. 1999;17:1061–70.PubMedGoogle Scholar
  47. 47.
    Hanauske AR, Degen D, Hilsenbeck SG, Bissery MC, Von Hoff DD. Effects of taxotere and taxol on in vitro colony formation of freshly explanted human tumor cells. Anticancer Drugs. 1992;3:121–4.PubMedGoogle Scholar
  48. 48.
    Valero V, Jones SE, Von Hoff DD, Booser DJ, Mennel RG, Ravdin PM, et al. A phase II study of docetaxel in patients with paclitaxel-resistant metastatic breast cancer. J Clin Oncol. 1998;16:3362–8.PubMedGoogle Scholar
  49. 49.
    Verschraegen CF, Sittisomwong T, Kudelka AP, Guedes E, Steger M, Nelson-Taylor T, et al. Docetaxel for patients with paclitaxel-resistant Mullerian carcinoma. J Clin Oncol. 2000;18:2733–9.PubMedGoogle Scholar
  50. 50.
    Bontenbal M, Creemers GJ, Braun HJ, de Boer AC, Janssen JT, Leys RB, et al. Phase II to III study comparing doxorubicin and docetaxel with fluorouracil, doxorubicin, and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer: results of a Dutch Community Setting Trial for the Clinical Trial Group of the Comprehensive Cancer Centre. J Clin Oncol. 2005;23:7081–8.PubMedGoogle Scholar
  51. 51.
    Nabholtz JM, Falkson C, Campos D, Szanto J, Martin M, Chan S, et al. Docetaxel and doxorubicin compared with doxorubicin and cyclophosphamide as first-line chemotherapy for metastatic breast cancer: results of a randomized, multicenter, phase III trial. J Clin Oncol. 2003;21:968–75.PubMedGoogle Scholar
  52. 52.
    Jassem J, Pienkowski T, Pluzanska A, Jelic S, Gorbunova V, Mrsic-Krmpotic Z, et al. Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: final results of a randomized phase III multicenter trial. J Clin Oncol. 2001;19:1707–15.PubMedGoogle Scholar
  53. 53.
    Gehl J, Boesgaard M, Paaske T, Vittrup Jensen B, Dombernowsky P. Combined doxorubicin and paclitaxel in advanced breast cancer: effective and cardiotoxic. Ann Oncol. 1996;7:687–93.PubMedGoogle Scholar
  54. 54.
    Gianni L, Viganò L, Locatelli A, Capri G, Giani A, Tarenzi E, et al. Human pharmacokinetic characterization and in vitro study of the interaction between doxorubicin and paclitaxel in patients with breast cancer. J Clin Oncol. 1997;15:1906–15.PubMedGoogle Scholar
  55. 55.
    Amadori D, Frassineti GL, Zoli W, Milandri C, Serra P, Tienghi A, et al. A phase I/II study; doxorubicin and paclitaxel (sequential combination) in the treatment of advanced breast cancer. Oncology. 1997;11:30–3.PubMedGoogle Scholar
  56. 56.
    Gianni L, Munzone E, Capri G, Fulfaro F, Tarenzi E, Villani F, et al. Paclitaxel by 3-hour infusion in combination with bolus doxorubicin in women with untreated metastatic breast cancer: high antitumor efficacy and cardiac effects in a dose-finding and sequence-finding study. J Clin Oncol. 1995;13:2688–99.PubMedGoogle Scholar
  57. 57.
    Dombernowsky P, Gehl J, Boesgaard M, Jensen TP, Jensen BV. Doxorubicin and paclitaxel, a highly active combination in the treatment of metastatic breast cancer. Semin Oncol. 1995;22(Suppl 15):13–7.PubMedGoogle Scholar
  58. 58.
    Biganzoli L, Cufer T, Bruning P, Coleman R, Duchateau L, Calvert AH, et al. Doxorubicin and paclitaxel versus doxorubicin and cyclophosphamide as first-line chemotherapy in metastatic breast cancer: The European Organization for Research and Treatment of Cancer 10961 multicenter phase III trial. J Clin Oncol. 2002;20:3114–21.PubMedGoogle Scholar
  59. 59.
    Biganzoli L, Cufer T, Bruning P, Coleman RE, Duchateau L, Rapoport B, et al. Doxorubicin-paclitaxel: a safe regimen in terms of cardiac toxicity in metastatic breast carcinoma patients. Results from a European Organization for Research and Treatment of Cancer multicenter trial. Cancer. 2003;97:40–5.PubMedGoogle Scholar
  60. 60.
    Gianni L, Dombernowsky P, Sledge G, Martin M, Amadori D, Arbuck SG, et al. Cardiac function following combination therapy with paclitaxel and doxorubicin: an analysis of 657 women with advanced breast cancer. Ann Oncol. 2001;12:1067–73.PubMedGoogle Scholar
  61. 61.
    Luck H, Thomssen C, Untch M, Kuhn W, Eidtmann H, du Bois A, et al. Multicenter phase III study in first line treatment of advanced metastatic breast cancer (ABC). Epirubicin/paclitaxel (ET) vs epirubicin/cyclophosphamide (EC). A study of the AGO Breast Cancer Group. J Clin Oncol. 2000;19:73a (Abstract 280).Google Scholar
  62. 62.
    Ghersi D, Wilcken N, Simes RJ. A systematic review of taxane-containing regimens for metastatic breast cancer. Br J Cancer. 2005;93:293–301.PubMedGoogle Scholar
  63. 63.
    Piccart-Gebhart MJ, Burzykowski T, Buyse M, Sledge G, Carmichael J, Lück HJ, et al. Taxanes alone or in combination with anthracyclines as first-line therapy of patients with metastatic breast cancer. J Clin Oncol. 2008;26:1980–6.PubMedGoogle Scholar
  64. 64.
    De Laurentiis M, Cancello G, D’Agostino D, Giuliano M, Giordano A, Montagna E, et al. Taxane-based combinations as adjuvant chemotherapy of early breast cancer: a meta-analysis of randomized trials. J Clin Oncol. 2008;26:44–53.PubMedGoogle Scholar
  65. 65.
    Martin M, Pienkowski T, Mackey J, Pawlicki M, Guastalla JP, Weaver C, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med. 2005;352:2302–13.PubMedGoogle Scholar
  66. 66.
    Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: national surgical adjuvant breast and bowel project protocol B-27. J Clin Oncol. 2006;24:2019–27.PubMedGoogle Scholar
  67. 67.
    Roché H, Fumoleau P, Spielmann M, Canon JL, Delozier T, Serin D, et al. Sequential adjuvant epirubicin-based and docetaxel chemotherapy for node-positive breast cancer patients: the FNCLCC PACS 01 Trial. J Clin Oncol. 2006;24:5664–71.PubMedGoogle Scholar
  68. 68.
    Kowalski RJ, Giannakakou P, Hamel E. Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel (Taxol®). J Biol Chem. 1997;272:2534–41.PubMedGoogle Scholar
  69. 69.
    Giannakakou P, Gussio R, Nogales E, Downing KH, Zaharevitz D, Bollbuck B, et al. A common pharmacophore for epothilones and taxanes: a molecular basis for drug resistance conferred by tubulin mutations in human cancer cells. Proc Natl Acad Sci. 2000;97:2904–9.PubMedGoogle Scholar
  70. 70.
    Lee FY, Borzilleri R, Fairchild CR, Kim SH, Long BH, Reventos-Suarez C, et al. BMS-247550: a novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor efficacy. Clin Cancer Res. 2001;7:1429–37.PubMedGoogle Scholar
  71. 71.
    Mani S, McDaid HM, Grossman A, Muggia F, Goel S, Griffin T, et al. Peripheral blood mononuclear and tumor cell pharmacodynamics of the novel epothilone analogue, ixabepilone. Ann Oncol. 2007;18:190–5.PubMedGoogle Scholar
  72. 72.
    Thomas E, Tabernero J, Fornier M, Conté P, Fumoleau P, Lluch A, et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in patients with taxane-resistant metastatic breast cancer. J Clin Oncol. 2007;25:3399–406.PubMedGoogle Scholar
  73. 73.
    Perez EA, Lerzo G, Pivot X, Thomas E, Vahdat L, Bosserman L, et al. Efficacy and safety of ixabepilone (BMS-247550) in a phase II study of patients with advanced breast cancer resistant to anthracycline, a taxane, and capecitabine. J Clin Oncol. 2007;25:3407–14.PubMedGoogle Scholar
  74. 74.
    Roché H, Yelle L, Cognetti F, Mauriac L, Bunnell C, Sparano J, et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, as first-line therapy in patients with metastatic breast cancer previously treated with anthracycline chemotherapy. J Clin Oncol. 2007;25:3415–20.PubMedGoogle Scholar
  75. 75.
    Denduluri N, Low JA, Lee JJ, Berman AW, Walshe JM, Vatas U, et al. Phase II trial of ixabepilone, an epothilone B analog, in patients with metastatic breast cancer previously untreated with taxanes. J Clin Oncol. 2007;25:3421–7.PubMedGoogle Scholar
  76. 76.
    Thomas ES, Gomez HL, Li RK, Chung HC, Fein LE, Chan VF, et al. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol. 2007;25:5210–7.PubMedGoogle Scholar
  77. 77.
    Lee FY, Camuso A, Castenada C, Flefleh I, Ingio D, Kan K, et al. Preclinical efficacy evaluation of ixabepilone (BMS-247550) in combination with cetuximab or capecitabine in human colon and lung carcinoma. J Clin Oncol. 2006;24:18s (Abstract 12017).Google Scholar
  78. 78.
    Korb T, Schlüter K, Enns A, Spiegel HU, Senninger N, Nicolson GL, et al. Integrity of actin fibers and microtubules influences metastatic tumor cell adhesion. Exp Cell Res. 2004;299:236–47.PubMedGoogle Scholar
  79. 79.
    Hill SA, Lonergan SJ, Denekamp J, Chaplin DJ. Vinca alkaloids: anti-vascular effects in a murine tumour. Eur J Cancer. 1993;9:1320–4.Google Scholar
  80. 80.
    Nihei Y, Suzuki M, Okano A, Tsuji T, Akiyama Y, Tsuruo T, et al. Evaluation of antivascular and antimitotic effects of tubulin binding agents in solid tumor therapy. Jpn J Cancer Res. 1999;90:1387–95.PubMedGoogle Scholar
  81. 81.
    Landuyt W, Verdoes O, Darius DO, Drijkoningen M, Nuyts S, Theys J, et al. Vascular targeting of solid tumours: a major “inverse” volume-response relationship following combretastatin A-4 phosphate treatment of rat rhabdomyosarcomas. Eur J Cancer. 2000;36:1833–43.PubMedGoogle Scholar
  82. 82.
    Tozer GM, Prise VE, Wilson J, Locke RJ, Vojnovic B, Stratford MR, et al. Combretastatin A-4 phosphate as a tumor vascular-targeting agent: early effects in tumors and normal tissues. Cancer Res. 1999;59:1626–34.PubMedGoogle Scholar
  83. 83.
    Holwell SE, Cooper PA, Thompson MJ, Pettit GR, Lippert LW 3rd, Martin SW, et al. Combretastatin A-1 phosphate a novel tubulin-binding agent with in vivo anti-vascular effects in experimental tumours. Anticancer Res. 2002;22:707–11.PubMedGoogle Scholar
  84. 84.
    Blakey DC, Ashton SE, Westwood FR, Walker M, Ryan AJ. ZD6126: a novel small molecule vascular targeting agent. Int J Radiat Oncol Biol Phys. 2002;54:1497–502.PubMedGoogle Scholar
  85. 85.
    Ching L-M, Joseph WR, Crosier KE, Baguley BC. Induction of tumor necrosis factor-alpha messenger RNA in human and murine cells by the flavone acetic acid analogue 5,6-dimethylxanthenone-4 acetic acid (NSC 640488). Cancer Res. 1994;54:870–2.PubMedGoogle Scholar
  86. 86.
    Bunge MB. The axonal cytoskeleton: its role in generating and maintaining cell form. Trends Neurosci. 1986;9:477–82.Google Scholar
  87. 87.
    Campenot RB, Lund K, Senger DL. Delivery of newly synthesized tubulin to rapidly growing distal axons of rat sympathetic neurons in compartmented cultures. J Cell Biol. 1996;135:701–9.PubMedGoogle Scholar
  88. 88.
    Mercken M, Fischer I, Kosik KS, Nixon RA. Three distinct axonal transport rates for tau, tubulin, and other microtubule-associated proteins. J Neurosci. 1995;15:8259–67.PubMedGoogle Scholar
  89. 89.
    Lobato RD. Historical vignette of Cajal’s work “Degeneration and regeneration of the nervous system” with a reflection of the author. Neurocirugia. 2008;19:456–68.PubMedGoogle Scholar
  90. 90.
    Yamada KM, Spooner BS, Wessells NK. Axon growth: roles of microfilaments and microtubules. Proc Natl Acad Sci USA. 1970;66:1206–12.PubMedGoogle Scholar
  91. 91.
    Hughes A. The growth of embryonic neurites; a study of cultures of chick neural tissues. J Anat. 1953;87:150–62.PubMedGoogle Scholar
  92. 92.
    Schlaepfer WW, Bruce J. Neurofilament proteins are distributed in a diminishing proximodistal gradient along rat sciatic nerve. J Neurochem. 1990;55:453–60.PubMedGoogle Scholar
  93. 93.
    Dent EW, Gertler FB. Cytoskeletal dynamics and transport in growth cone motility and axon guidance. Neuron. 2003;40:209–27.PubMedGoogle Scholar
  94. 94.
    Te Loo DM, van Schie RM, Hoogerbrugge PM. Effect of azole antifungal therapy on vincristine toxicity in childhood acute lymphoblastic leukemia. J Clin Oncol. 2009;27:15s (Abstract 10049).Google Scholar
  95. 95.
    Al Ferayan A, Russell NA, Al Wohaibi M, Awada A, Scherman B. Cerebrospinal fluid lavage in the treatment of inadvertent intrathecal vincristine injection. Childs Nerv Syst. 1999;15:87–9.PubMedGoogle Scholar
  96. 96.
    Neuwelt EA. Mechanisms of disease: the blood-brain barrier. Neurosurgery. 2004;54:131–42.PubMedGoogle Scholar
  97. 97.
    Rowinsky EK, Burke PJ, Karp JE, Tucker RW, Ettinger DS, Donehower RC. Phase I study of taxol in refractory adult acute leukemia. Cancer Res. 1989;49:4640–7.PubMedGoogle Scholar
  98. 98.
    Ertürk A, Hellal F, Enes J, Bradke F. Disorganized microtubules underlie the formation of retraction bulbs and the failure of axonal regeneration. J Neurosci. 2007;27:9169–80.PubMedGoogle Scholar
  99. 99.
    Murphy DB, Borisy GG. Association of high-molecular-weight proteins with microtubules and their role in microtubule assembly in vitro. Proc Natl Acad Sci USA. 1975;72:2696–700.PubMedGoogle Scholar
  100. 100.
    Levi-Montalcini R, Booker B. Excessive growth of the sympathetic ganglia evoked by a protein isolated from mouse salivary glands. Proc Natl Acad Sci USA. 1960;46:373–84.PubMedGoogle Scholar
  101. 101.
    Vickers JC, Morrison JH, Friedrich VL Jr, Elder GA, Perl DP, Katz RN, et al. Age-associated and cell-type-specific neurofibrillary pathology in transgenic mice expressing the human midsized neurofilament subunit. J Neurosci. 1994;14:5603–12.PubMedGoogle Scholar
  102. 102.
    Svitkina TM, Verkhovsky AB, Borisy GG. Plectin sidearms mediate interaction of the intermediate filaments with microtubules and other components of the cytoskeleton. J Cell Biol. 1996;135:991–1007.PubMedGoogle Scholar
  103. 103.
    Stanley JR. Cell adhesion molecules as targets of autoantibodies in pemphigus and pemphigoid, bullous diseases due to defective epidermal cell adhesion. Adv Immunol. 1993;53:291–325.PubMedGoogle Scholar
  104. 104.
    Lee S, Yang W, Lan KH, Sellappan S, Klos K, Hortobagyi G, et al. Enhanced sensitization to taxol-induced apoptosis by herceptin pretreatment in ErbB2-overexpressing breast cancer cells. Cancer Res. 2002;62:5703–10.PubMedGoogle Scholar
  105. 105.
    Tanaka K, Iwamoto S, Gon G, Nohara T, Iwamoto M, Tanigawa N. Expression of survivin and its relationship to loss of apoptosis in breast carcinomas. Clin Cancer Res. 2000;6:127–34.PubMedGoogle Scholar
  106. 106.
    Xia W, Bisi J, Strum J, Liu L, Carrick K, Graham KM, et al. Regulation of survivin by HER2 signaling: therapeutic implications for ErbB2-overexpressing breast cancers. Cancer Res. 2006;66:1640–7.PubMedGoogle Scholar
  107. 107.
    Tassone P, Tagliaferri P, Perricelli A, Blotta S, Quaresima B, Martelli ML, et al. BRCA1 expression modulates chemosensitivity of BRCA1-defective HCC1937 human breast cancer cells. Br J Cancer. 2003;88:1285–91.PubMedGoogle Scholar
  108. 108.
    Moritz M, Braunfeld MB, Sedat JW, Alberts B, Agard DA. Microtubule nucleation by gamma-tubulin-containing rings in the centrosome. Nature. 1995;378:638–40.PubMedGoogle Scholar
  109. 109.
    Dutertre S, Descamps S, Prigent C. On the role of aurora-A in centrosome function. Oncogene. 2002;21:6175–83.PubMedGoogle Scholar
  110. 110.
    Anand S, Penrhyn-Lowe S, Venkitaraman AR. Aurora-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to taxol. Cancer Cell. 2003;3:51–62.PubMedGoogle Scholar
  111. 111.
    Brooks TA, Minderman H, O’Loughlin KL, Pera P, Ojima I, Baer MR, et al. Taxane-based reversal agents modulate drug resistance mediated by P-glycoprotein, multidrug resistance protein, and breast cancer resistance protein. Mol Cancer Ther. 2003;2:1195–205.PubMedGoogle Scholar
  112. 112.
    Chaudhary PM, Roninson IB. Expression and activity of P-glycoprotein, a multidrug efflux pump, in human hematopoieitc cells. Cell. 1991;66:85–94.PubMedGoogle Scholar
  113. 113.
    Licht T, Pastan I, Gottesman M, Herrman F. P-glycoprotein-mediated multidrug resistance in normal and neoplastic hematopoietic cells. Ann Hematol. 1994;69:159–71.PubMedGoogle Scholar
  114. 114.
    Dumontet C, Jordan MA, Lee FF. Ixabepilone: targeting betaIII-tubulin expression in taxane-resistant malignancies. Mol Cancer Ther. 2009;8:17–25.PubMedGoogle Scholar
  115. 115.
    Gonçalves A, Braguer D, Kamath K, Martello L, Briand C, Horwitz S, et al. Resistance to Taxol in lung cancer cells associated with increased microtubule dynamics. Proc Natl Acad Sci USA. 2001;98:11737–42.PubMedGoogle Scholar
  116. 116.
    Fujimoto-Ouchi K, Sekiguchi F, Yamamoto K, Shirane M, Yamashita Y, Mori K. Preclinical study of prolonged administration of trastuzumab as combination therapy after disease progression during trastuzumab monotherapy. Cancer Chemother Pharmacol. 2010;66:269–76.PubMedGoogle Scholar
  117. 117.
    Yamaguchi H, Paranawithana SR, Lee MW, Huang Z, Bhalla KN, Wang HG. Epothilone B analogue (BMS-247550)-mediated cytotoxicity through induction of Bax conformational change in human breast cancer cells. Cancer Res. 2002;62:466–71.PubMedGoogle Scholar
  118. 118.
    Huang Y, Ray S, Reed JC, Ibrado AM, Tang C, Nawabi A, et al. Estrogen increases intracellular p26Bcl-2 to p21Bax ratios and inhibits taxol-induced apoptosis of human breast cancer MCF-7 cells. Breast Cancer Res Treat. 1997;42:73–81.PubMedGoogle Scholar
  119. 119.
    Lee SH, Son SM, Son DJ, Kim SM, Kim TJ, Song S, et al. Epothilones induce human colon cancer SW620 cell apoptosis via the tubulin polymerization-independent activation of the nuclear factor-κB/IκB kinase signal pathway. Mol Cancer Ther. 2007;6:2786–97.PubMedGoogle Scholar
  120. 120.
    Nakahara C, Nakamura K, Yamanaka N, Baba E, Wada M, Matsunaga H, et al. Cyclosporine-A enhances docetaxel-induced apoptosis through inhibition of nuclear factor-κB activation in human gastric carcinoma cells. Clin Cancer Res. 2003;9:5409–16.PubMedGoogle Scholar
  121. 121.
    Huang Y, Fang Y, Dziadyk JM, Norris JS, Fan W. The possible correlation between activation of NF-κB/IκB pathway and the susceptibility of tumor cells to paclitaxel-induced apoptosis. Oncol Res. 2002;13:113–22.PubMedGoogle Scholar
  122. 122.
    Huang Y, Fang Y, Wu J, Dziadyk JM, Zhu X, Sui M, et al. Regulation of vinca alkaloid-induced apoptosis by NF-κB/IκB pathway in human tumor cells. Mol Cancer Ther. 2004;3:271–7.PubMedGoogle Scholar
  123. 123.
    MacKeigan JP, Collins TS, Ting JP. MEK inhibition enhances paclitaxel-induced tumor apoptosis. J Biol Chem. 2000;275:38953–6.PubMedGoogle Scholar
  124. 124.
    Nicholson KM, Anderson NG. The protein kinase B/Akt signaling pathway in human malignancy. Cell Signal. 2002;14:381–95.PubMedGoogle Scholar
  125. 125.
    Fujino L, Bali P, Wittmann S, Donapaty S, Guo F, Yamaguchi H, et al. Histone deactylase inhibitor LAQ824 down-regulates Her-2 and sensitizes human breast cancer cells to trastuzumab, taxotere, gemcitabine, and epothilone B. Mol Cancer Ther. 2003;2:971–84.Google Scholar
  126. 126.
    Sorlie T, Tibshirani R, Parker J, Hastie T, Marron JS, Nobel A, et al. Repeated observation of breast tumor subtypes in independent gene expression data sets. Proc Natl Acad Sci USA. 2003;100:8418–23.PubMedGoogle Scholar
  127. 127.
    Sørlie T, Perou CM, Tibshirani R, Aas T, Geisler S, Johnsen H, et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci USA. 2001;98:10869–74.PubMedGoogle Scholar
  128. 128.
    Finnegan TJ, Carey LA. Gene-expression analysis and the basal-like breast cancer subtype. Future Oncol. 2007;3:55–63.PubMedGoogle Scholar
  129. 129.
    Rouzier R, Perou CM, Symmans WF, Ibrahim N, Cristofanilli M, Anderson K, et al. Breast cancer molecular subtypes respond differently to preoperative chemotherapy. Clin Cancer Res. 2005;11:5678–85.PubMedGoogle Scholar
  130. 130.
    Liedtke C, Mazouni C, Hess KR, André F, Tordai A, Mejia JA, et al. Response to neoadjuvant therapy and long-term survival in patients with triple-negative breast cancer. J Clin Oncol. 2008;26:1275–81.PubMedGoogle Scholar
  131. 131.
    Baselga J, Zambetti M, Llombart-Cussac A, Manikhas G, Kubista E, Steger GG, et al. Phase II genomics study of ixabepilone as neoadjuvant treatment for breast cancer. J Clin Oncol. 2009;27:526–34.PubMedGoogle Scholar
  132. 132.
    Henderson IC, Berry DA, Demetri GD, Cirrincione CT, Goldstein LJ, Martino S, et al. Improved outcomes from adding sequential paclitaxel but not from escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer. J Clin Oncol. 2003;21:976–83.PubMedGoogle Scholar
  133. 133.
    Baselga J, Albanell J, Ruiz A, Lluch A, Gascón P, Guillém V, et al. Phase II and tumor pharmacodynamic study of gefitinib in patients with advanced breast cancer. J Clin Oncol. 2005;23:5323–33.PubMedGoogle Scholar
  134. 134.
    von Minckwitz G, Jonat W, Fasching P, du Bois A, Kleeberg U, Lück HJ, et al. A multicentre phase II study on geftinib in taxane- and anthracycline-pretreated metastatic breast cancer. Breast Cancer Res Treat. 2005;89:165–72.Google Scholar
  135. 135.
    Geyer CE, Forster J, Lindquist D, Chan S, Romieu CG, Pienkowski T, et al. Lapatinib plus capecitabine for HER2-positive advanced breast cancer. N Engl J Med. 2006;355:2733–43.PubMedGoogle Scholar
  136. 136.
    Fujiwara Y, Hosokawa Y, Watanabe K, Tanimura S, Ozaki K, Kohno M. Blockade of the phosphatidylinositol-3-kinase/Akt signaling pathway enhances the induction of apoptosis by microtubule-destabilizing agents in tumor cells in which the pathway is constitutively activated. Mol Cancer Ther. 2007;6:1133–42.PubMedGoogle Scholar
  137. 137.
    Brognard J, Clark AS, Ni Y, Dennis PA. Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. Cancer Res. 2001;61:3986–97.PubMedGoogle Scholar
  138. 138.
    Baas PW, Qiang L. Neuronal microtubules: when the MAP is the roadblock. Trends Cell Biol. 2005;4:183–7.Google Scholar
  139. 139.
    Failly M, Korur S, Egler V, Boulay JL, Lino MM, Imber R, et al. Combination of sublethal concentrations of epidermal growth factor receptor inhibitor and microtubule stabilizer induces apoptosis of glioblastoma cells. Mol Cancer Ther. 2007;6:773–81.PubMedGoogle Scholar
  140. 140.
    Semenza GL. Hypoxia-inducible factor 1: control of oxygen homeostasis in health and disease. Pediatr Res. 2001;49:614–7.PubMedGoogle Scholar
  141. 141.
    Flügel D, Görlach A, Michiels C, Kietzmann T. Glycogen synthase kinase 3 phosphorylates hypoxia-inducible factor 1α and mediates its destabilization in a VHL-independent manner. Mol Cell Biol. 2007;27:3253–65.PubMedGoogle Scholar

Copyright information

© The Japanese Breast Cancer Society 2010

Authors and Affiliations

  1. 1.Mary Babb Randolph Cancer CenterWest Virginia University Schools of Pharmacy and MedicineMorgantownUSA
  2. 2.Robert C. Byrd Health Sciences CenterMorgantownUSA

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