Skip to main content
SpringerLink
Log in
Book cover

Drug Management of Prostate Cancer pp 179–194Cite as

Microtubule Targeting Agents

  • Chapter
  • First Online:

Abstract

Microtubules are intracellular filamentous structures that comprise the cytoskeleton of all eukaryotic cells. They play a critical role in various cellular processes such as mitosis and have become an essential target for the chemotherapeutic approach to a wide spectrum of malignancies. It is thus crucial to understand the basic biology of the microtubule and be familiar with the various microtubule targeting agents used clinically. This chapter provides an overview of microtubule physiology and the novel microtubule-targeting chemotherapeutic agents that are currently being evaluated for the treatment of taxane-refractory, castration-resistant prostate cancer.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Hamel E, Covell DG. Antimitotic peptides and depsipeptides. Curr Med Chem Anticancer Agents 2002;2:19–53.

    PubMed  CAS  Google Scholar 

  2. Jordan MA. Mechanism of action of antitumor drugs that interact with microtubules and tubulin. Curr Med Chem Anticancer Agents 2002;2:1–17.

    PubMed  CAS  Google Scholar 

  3. Jordan MA, Wilson L. Microtubules as a target for anticancer drugs. Nat Rev Cancer 2004;4:253–65.

    PubMed  CAS  Google Scholar 

  4. Jimenez-Barbero J, Amat-Guerri F, Snyder JP. The solid state, solution and tubulin-bound conformations of agents that promote microtubule stabilization. Curr Med Chem Anticancer Agents 2002;2(1):91–122.

    PubMed  CAS  Google Scholar 

  5. Desai A, Mitchison TJ. Microtubule polymerization dynamics. Annu Rev Cell Dev Biol 1997;13:83–117.

    PubMed  CAS  Google Scholar 

  6. Oakley BR. An abundance of tubulins. Trends Cell Biol 2000;10:537–42.

    PubMed  CAS  Google Scholar 

  7. Sharp DJ, Rogers GC, Scholey JM. Microtubule motors in mitosis. Nature 2000;407:41–7.

    PubMed  CAS  Google Scholar 

  8. Calvert PM, O’Neill V, Twelves C, et al. A phase I clinical and pharmacokinetic study of EPO906 (Epothilone B), given every three weeks, in patients with advanced solid tumors. Proc Am Soc Clin Oncol 2001;20:A429.

    Google Scholar 

  9. Wilson L, Jordan MA. Pharmacological probes of microtubule function. In: Hyams J, Lloyd C, editors. Microtubules. New York: Wiley; 1994. p. 59–84.

    Google Scholar 

  10. Jordan MA, Wilson L. The use of drugs to study the role of microtubule assembly dynamics in living cells, Molecular motors and the cytoskeleton. Methods Enzymol, vol. 298. 1998. p. 252–76.

    Google Scholar 

  11. Lobert S, Correia J. Energetics of vinca alkaloid interactions with tubulin. Methods Enzymol 2000;323:77–103.

    PubMed  CAS  Google Scholar 

  12. Bai RB, Pettit GR, Hamel E. Dolastatin 10. a powerful cytostatic peptide derived from a marine animal. Inhibition of tubulin polymerization mediated through the vinca alkaloid binding domain. Biochem Pharmacol 1990;39:1941–9.

    PubMed  CAS  Google Scholar 

  13. Bai RB, Pettit GR, Hamel E. Binding of dolastatin 10 to tubulin at a distinct site for peptide antimitotic agents near the exchangeable nucleotide and vinca alkaloid sites. J Biol Chem 1990;265:17141–9.

    PubMed  CAS  Google Scholar 

  14. Wilson L, Jordan MA, Morse A, Margolis RL. Interaction of vinblastine with steady-state microtubules in vitro. J Mol Biol 1982;159:129–49.

    Google Scholar 

  15. Correia JJ, Lobert S. Physiochemical aspects of tubulin-interacting antimitotic drugs. Curr Pharm Des 2001;7(13):1213–28.

    PubMed  CAS  Google Scholar 

  16. Na GC, Timasheff SN. Thermodynamic linkage between tubulin self-association and the binding of vinblastine. Biochemistry 1980;19(7):1347–54.

    PubMed  CAS  Google Scholar 

  17. Jordan MA, Margolis RL, Himes RH, Wilson L. Identification of a distinct class of vinblastine binding sites on microtubules. J Mol Biol 1986;187:61–73.

    PubMed  CAS  Google Scholar 

  18. Singer WD, Jordan MA, Wilson L, Himes RH. Binding of vinblastine to stabilized microtubules. Mol Pharmacol 1989;36(3):366–70.

    PubMed  CAS  Google Scholar 

  19. Panda D, Jordan MA, Chin K, Wilson L. Differential effects of vinblastine on polymerization and dynamics at opposite microtubule ends. J Biol Chem 1996;271:29807–12.

    PubMed  CAS  Google Scholar 

  20. Panda D, Miller H, Wilson L. Determination of the size and chemical nature of the stabilizing cap at microtubule ends using modulators of polymerization dynamics. Biochemistry 2002;41:1609–17.

    PubMed  CAS  Google Scholar 

  21. Hastie SB. Interactions of colchicine with tubulin. Pharmacol Ther 1991;512:377–401.

    Google Scholar 

  22. Sternlicht H, Ringel I. Colchicine inhibition of microtubule assembly via copolymer formations. J Biol Chem 1979;254:10540–50.

    PubMed  CAS  Google Scholar 

  23. Sternlicht H, Ringel I, Szasz J. Theory for modelling the copolymerization of tubulin and tubulin-colchicine complex. Biophys J 1983;42:255–67.

    PubMed  CAS  Google Scholar 

  24. Farrell KW, Wilson L. The differential kinetic stabilization of opposite microtubule ends by tubulin–colchicine complexes. Biochemistry 1984;23:3741–8.

    PubMed  CAS  Google Scholar 

  25. Skoufias D, Wilson L. Mechanism of inhibition of microtubule polymerization by colchicine: inhibitory potencies of unliganded colchicine and tubulin–colchicine complexes. Biochemistry 1992;31:738–46.

    PubMed  CAS  Google Scholar 

  26. Margolis RL, Rauch CT, Wilson L. Mechanism of colchicine dimer addition to microtubule ends: implications for the microtubule polymerization mechanism. Biochemistry 1980;19:5550–7.

    PubMed  CAS  Google Scholar 

  27. Wilson L, Farrell KW. Kinetics and steady-state dynamics of tubulin addition and loss at opposite microtubule ends: the mechanism of action of colchicine. Ann N Y Acad Sci 1986;466:690–708.

    PubMed  CAS  Google Scholar 

  28. Panda D, Goode BL, Feinstein SC, Wilson L. Kinetic stabilization of microtubule dynamics at steady state by tau and microtubule-binding domains of tau. Biochemistry 1995;34:11117–27.

    PubMed  CAS  Google Scholar 

  29. Jordan A, Hadfield JA, Lawrence NJ, et al. Tubulin as a target for anticancer drugs: agents which interact with the mitotic spindle. Med Res Rev 1998;18:259–96.

    PubMed  CAS  Google Scholar 

  30. Pettit GR, Cragg GM, Singh SB. Antineoplastic agents, 122. Constituents ofCombretum caffrum. J Nat Prod 1987;50:386–91.

    PubMed  CAS  Google Scholar 

  31. Tozer GM, Kanthou C, Parkins CS, et al. The biology of the combretastatins as tumour vascular targeting agents. Int J Exp Pathol 2002;83:21–38.

    PubMed  CAS  Google Scholar 

  32. Pettit GR, Temple Jr C, Narayanan VL, et al. Antineoplastic agents 322. Synthesis of combretastatin A-4 prodrugs. Anticancer Drug Des 1995;10:299–309.

    PubMed  CAS  Google Scholar 

  33. Dark GG, Hill SA, Prise VE, et al. Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature. Cancer Res 1997;57:1829–34.

    PubMed  CAS  Google Scholar 

  34. Ahmed B, Van Eijk LI, Bouma-Ter Steege JC, et al. Vascular targeting effect of combretastatin A-4 phosphate dominates the inherent angiogenesis inhibitory activity. Int J Cancer 2003;105:20–5.

    PubMed  CAS  Google Scholar 

  35. Schumacher G, Neuhaus P. The physiological estrogen metabolite 2-methoxyestradiol reduces tumor growth and induces apoptosis in human solid tumors. J Cancer Res Clin Oncol 2001;127:405–10.

    PubMed  CAS  Google Scholar 

  36. D’Amato RJ, Lin CM, Flynn E, et al. 2-Methoxyestradiol, an endogenous mammalian metabolite, inhibits tubulin polymerization by interacting at the colchicine site. Proc Natl Acad Sci U S A 1994;91:3964–8.

    PubMed  Google Scholar 

  37. Fotsis T, Zhang Y, Pepper MS, et al. The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth. Nature 1994;368:237–9.

    PubMed  CAS  Google Scholar 

  38. de Ines C, Leynadier D, Barasoain I, et al. Inhibition of microtubules and cell cycle arrest by a new 1-deaza-7, 8-dihydropteridine antitumor drug, CI 980, and by its chiral isomer, NSC 613863. Cancer Res 1994;54:75–84.

    PubMed  Google Scholar 

  39. Waud WR, Leopold WR, Elliott WL, et al. Antitumor activity of ethyl 5-amino-1,2-dihydro-2-methyl-3-phenyl-pyrido [3,4-b]pyrazin-7-ylcarbamate, 2-hydroxyethanesulfonate, hydrate (NSC 370147) against selected tumor systems in culture and in mice. Cancer Res 1990;50:3239–44.

    PubMed  CAS  Google Scholar 

  40. Verdier-Pinard P, Kepler JA, Pettit GR, Hamel E. Sustained intracellular retention of dolastatin 10 causes its potent antimitotic activity. Mol Pharmacol 2000;57:180–7.

    PubMed  CAS  Google Scholar 

  41. Singer WD, Hersh RT, Himes RH. Effect of solution variables on the binding of vinblastine to tubulin. Biochem Pharmacol 1988;37:2691–6.

    PubMed  CAS  Google Scholar 

  42. Bai R, Taylor GF, Schmidt JM, Williams MD, Kepler JA, Pettit GR, et al. Interaction of dolastatin 10 with tubulin: Induction of aggregation and binding and dissociation reactions. Mol Pharmacol 1995;47:965–76.

    PubMed  CAS  Google Scholar 

  43. Safa AR, Hamel E, Felsted RL. Photoaffinity labeling of tubulin subunits with a photoactive analogue of vinblastine. Biochemistry 1987;26:97–102.

    PubMed  CAS  Google Scholar 

  44. Bai RL, Pettit GR, Hamel E. Structure-activity studies with chiral isomers and with segments of the antimitotic marine peptide dolastatin 10. Biochem Pharmacol 1990;40:1859–64.

    PubMed  CAS  Google Scholar 

  45. Bai R, Roach MC, Jayaram SK, et al. Differential effects of active isomers, segments, and analogs of dolastatin 10 on ligand interactions with tubulin. Correlation with cytotoxicity. Biochem Pharmacol 1993;45:1503–15.

    PubMed  CAS  Google Scholar 

  46. Pettit GR, Srirangam JK, Barkoczy J, et al. Antineoplastic agents 337. Synthesis of dolastatin 10 structural modifications. Anticancer Drug Des 1995;10:529–44.

    PubMed  CAS  Google Scholar 

  47. Li Y, Kobayashi H, Hashimoto Y, et al. Interaction of marine toxin dolastatin 10 with porcine brain tubulin: competitive inhibition of rhizoxin and phomopsin A binding. Chem Biol Interact 1994;93:175–83.

    PubMed  Google Scholar 

  48. Otani M, Natsume T, Watanabe JI, et al. TZT-1027, an antimicrotubule agent, attacks tumor vasculature and induces tumor cell death. Jpn J Cancer Res 2000;91:837–44.

    PubMed  CAS  Google Scholar 

  49. Natsume T, Watanabe J, Tamaoki S, et al. Characterization of the interaction of TZT-1027, a potent antitumor agent, with tubulin. Jpn J Cancer Res 2000;91:737–47.

    PubMed  CAS  Google Scholar 

  50. Wani MC, Taylor HL, Wall ME, Coggan P, McPhail AT. Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent fromTaxus brevifolia. J Am Chem Soc 1971;93:2325–7.

    PubMed  CAS  Google Scholar 

  51. Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol. Nature 1979;277:665–7.

    PubMed  CAS  Google Scholar 

  52. Schiff PB, Horwitz SB. Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci U S A 1980;77:1561–5.

    PubMed  CAS  Google Scholar 

  53. Schiff PB, Horwitz SB. Taxol assembles tubulin in the absence of exogenous guanosine 5′-triphosphate or microtubule-associated proteins. Biochemistry 1981;20:3247–52.

    PubMed  CAS  Google Scholar 

  54. Diaz JF, Valpuesta JM, Chacon P, Diakun G, Andreu JM. Changes in microtubule protofilament number induced by Taxol binding to an easily accessible site. Internal microtubule dynamics. J Biol Chem 1998;273:33803–10.

    PubMed  CAS  Google Scholar 

  55. Parness J, Horwitz SB. Taxol binds to polymerized tubulin in vitro. J Cell Biol 1981;91:479–87.

    PubMed  CAS  Google Scholar 

  56. Rao S, Horwitz SB, Ringel I. Direct photoaffinity labeling of tubulin with taxol. J Natl Cancer Inst 1992;84:785–8.

    PubMed  CAS  Google Scholar 

  57. Lowe J, Li H, Downing KH, Nogales E. Refined structure of alpha beta-tubulin at 3.5 Å resolution. J Mol Biol 2001;313:1045–57.

    PubMed  CAS  Google Scholar 

  58. Jordan MA, Toso RJ, Thrower D, Wilson L. Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. Proc Natl Acad Sci U S A 1993;90:9552–6.

    PubMed  CAS  Google Scholar 

  59. Derry WB, Wilson L, Jordan MA. Substoichiometric binding of taxol suppresses microtubule dynamics. Biochemistry 1995;34:2203–11.

    PubMed  CAS  Google Scholar 

  60. Chen JG, Horwitz SB. Differential mitotic responses to microtubule-stabilizing and -destabilizing drugs. Cancer Res 2002;62:1935–8.

    PubMed  CAS  Google Scholar 

  61. Torres K, Horwitz SB. Mechanisms of taxol-induced cell death are concentration dependent. Cancer Res 1998;58:3620–6.

    PubMed  CAS  Google Scholar 

  62. 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.

    PubMed  CAS  Google Scholar 

  63. Rao S, Orr GA, Chaudhary AG, Kingston DG, Horwitz SB. Characterization of the taxol binding site on the microtubule. 2-(m-Azidobenzoyl)taxol photolabels a peptide (amino acids 217-231) of beta-tubulin. J Biol Chem 1995;270:20235–8.

    PubMed  CAS  Google Scholar 

  64. Orr GA, Rao S, Swindell CS, Kingston DG, Horwitz SB. Photoaffinity labeling approach to map the taxol-binding site on the microtubule. Methods Enzymol 1998;298:238–52.

    PubMed  CAS  Google Scholar 

  65. Rao S, He L, Chakravarty S, Ojima I, Orr GA, Horwitz SB. Characterization of the taxol binding site on the microtubule. Identification of Arg(282) in beta-tubulin as the site of photoincorporation of a 7-benzophenone analogue of taxol. J Biol Chem 1999;274:37990–4.

    PubMed  CAS  Google Scholar 

  66. Rao S, Aberg F, Nieves E, Horwitz SB, Orr GA. Identification by mass spectrometry of a new alpha-tubulin isotype expressed in human breast and lung carcinoma cell lines. Biochemistry 2001;40:2096–103.

    PubMed  CAS  Google Scholar 

  67. Nogales E, Wolf SG, Downing KH. Structure of the alpha beta tubulin dimer by electron crystallography. Nature 1998;391:199–203. erratum in: Nature 393:191.

    PubMed  CAS  Google Scholar 

  68. Bollag DM, McQueney PA, Zhu J, Hensens O, Koupal L, Liesch J, et al. Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action. Cancer Res 1995;55:2325–33.

    PubMed  CAS  Google Scholar 

  69. ter Haar E, Kowalski RJ, Hamel E, Lin CM, Longley RE, Gunasekera SP, et al. Discodermolide, a cytotoxic marine agent that stabilizes microtubules more potently than taxol. Biochemistry 1996;35:243–50.

    PubMed  Google Scholar 

  70. He L, Orr GA, Horwitz SB. Novel molecules that interact with microtubules and have functional activity similar to taxol. Drug Discov Today 2001;6:1153–64.

    PubMed  CAS  Google Scholar 

  71. Hung DT, Chen J, Schreiber SL. (+)-Discodermolide binds to microtubules in stoichiometric ratio to tubulin dimers, blocks taxol binding and results in mitotic arrest. Chem Biol 1996;3:287–93.

    PubMed  CAS  Google Scholar 

  72. Kowalski RJ, Giannakakou P, Gunasekera SP, Longley RE, Day BW, Hamel E. The microtubule-stabilizing agent discodermolide competitively inhibits the binding of paclitaxel (Taxol) to tubulin polymers, enhances tubulin nucleation reactions more potently than paclitaxel, and inhibits the growth of paclitaxel-resistant cells. Mol Pharmacol 1997;52:613–22.

    PubMed  CAS  Google Scholar 

  73. Long BH, Carboni JM, Wasserman AJ, Cornell LA, Casazza AM, Jensen PR, et al. Eleutherobin, a novel cytotoxic agent that induces tubulin polymerization, is similar to paclitaxel (taxol). Cancer Res 1998;58:1111–5.

    PubMed  CAS  Google Scholar 

  74. Hamel E, Sackett DL, Vourloumis D, Nicolaou KC. The coral-derived natural products eleutherobin and sarcodictyins A and B: effects on the assembly of purified tubulin with and without microtubule-associated proteins and binding at the polymer taxoid site. Biochemistry 1999;38:5490–8.

    PubMed  CAS  Google Scholar 

  75. Mooberry SL, Tien G, Hernandez AH, Plubrukarn A, Davison BS. Laulimalide and isolaulimalide, new paclitaxel-like microtubule-stabilizing agents. Cancer Res 1999;59:653–60.

    PubMed  CAS  Google Scholar 

  76. Pryor DE, O’Brate A, Bilcer G, Diaz JF, Wang Y, Kabaki M, et al. The microtubule stabilizing agent laulimalide does not bind in the taxoid site, kills cells resistant to paclitaxel and epothilones, and may not require its epoxide moiety for activity. Biochemistry 2002;41:9109–15.

    PubMed  CAS  Google Scholar 

  77. Pineda O, Farras J, Maccari L, Manetti F, Botta M, Vilarrasa J. Computational comparison of microtubule-stabilising agents laulimalide and peloruside with taxol and colchicine. Bioorg Med Chem Lett 2004;14:4825–9.

    PubMed  CAS  Google Scholar 

  78. Fojo AT, Whang-Peng J, Gottesman MM, Pastan I. Amplification of DNA sequences in human multidrug-resistant KB carcinoma cells. Proc Natl Acad Sci U S A 1985;82:7661–5.

    PubMed  CAS  Google Scholar 

  79. Hari M, Wang Y, Veeraraghavan S, Cabral F. Mutations in alpha- and beta-tubulin that stabilize microtubules and confer resistance to colcemid and vinblastine. Mol Cancer Ther 2003;2:597–605.

    PubMed  CAS  Google Scholar 

  80. Giannakakou P, Sackett DL, Kang YK, Zhan Z, Buters JT, Fojo T, et al. Paclitaxel-resistant human ovarian cancer cells have mutant beta-tubulins that exhibit impaired paclitaxel-driven polymerization. J Biol Chem 1997;272:17118–25.

    PubMed  CAS  Google Scholar 

  81. Giannakakou P, Sackett DL, Ward Y, Webster KR, Blagosklonny MV, Fojo T. p53 is associated with cellular microtubules and is transported to the nucleus by dynein. Nat Cell Biol 2000;2:709–17.

    PubMed  CAS  Google Scholar 

  82. Hari M, Loganzo F, Annable T, Tan X, Musto S, Morilla DB, et al. Paclitaxel-resistant cells have a mutation in the paclitaxel-binding region of beta-tubulin (Asp26Glu) and less stable microtubules. Mol Cancer Ther 2006;5:270–8.

    PubMed  CAS  Google Scholar 

  83. Cabral FR, Brady RC, Schibler MJ. A mechanism of cellular resistance to drugs that interfere with microtubule assembly. Ann N Y Acad Sci 1986;466:745–56.

    PubMed  CAS  Google Scholar 

  84. Cabral F, Barlow SB. Mechanisms by which mammalian cells acquire resistance to drugs that affect microtubule assembly. FASEB J 1989;3:1593–9.

    PubMed  CAS  Google Scholar 

  85. Minotti AM, Barlow SB, Cabral F. Resistance to antimitotic drugs in Chinese hamster ovary cells correlates with changes in the level of polymerized tubulin. J Biol Chem 1991;266:3987–94.

    PubMed  CAS  Google Scholar 

  86. Wilson L, Jordan MA. Microtubule dynamics: taking aim at a moving target. Chem Biol 1995;2:569–73.

    PubMed  CAS  Google Scholar 

  87. Jordan MA, Wilson L. Microtubules and actin filaments: dynamic targets for cancer chemotherapy. Curr Opin Cell Biol 1998;10:123–30.

    PubMed  CAS  Google Scholar 

  88. Goncalves 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 U S A 2001;98:11737–42.

    PubMed  CAS  Google Scholar 

  89. Fojo AT, Menefee M. Microtubule targeting agents: basic mechanisms of multidrug resistance (MDR). Semin Oncol 2005;32:S3–8.

    PubMed  CAS  Google Scholar 

  90. Jemal A, Siegel R, Ward E, et al. Cancer Statistics, CA Cancer. J Clin 2009;59:225–49.

    Google Scholar 

  91. Tannock IF, de Wit R, Berry W, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer. N Engl J Med 2004;351:1502–12.

    PubMed  CAS  Google Scholar 

  92. Petrylak DP, Tangen CM, Hussain M, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004;351:1513–20.

    PubMed  CAS  Google Scholar 

  93. Dawson N. Epothilones in prostate cancer: review of clinical experience. Ann Oncol 2007;18 Suppl 5:v22–7.

    PubMed  Google Scholar 

  94. Lee JJ, Kelly WK. Epothilones: tubulin polymerization as a novel target for prostate cancer therapy. Nat Clin Pract Oncol 2009;6(2):85–92.

    PubMed  CAS  Google Scholar 

  95. Beardsley EK, Chi KN. Systemic therapy after first-line docetaxel in metastatic castration-resistant prostate cancer. Curr Opin Support Palliat Care 2008;2:161–6.

    PubMed  Google Scholar 

  96. Rivera E, Lee J, Davies A. Clinical development of ixabepilone and other epothilones in patients with advanced solid tumors. Oncologist 2008;13:1207–23.

    PubMed  CAS  Google Scholar 

  97. Sepp-Lorenzino L, Balog A, Su DS, et al. The microtubule-stabilizing agents epothilones A and B and their desoxy-derivatives induce mitotic arrest and apoptosis in human prostate cancer cells. Prostate Cancer Prostatic Dis 1999;2:41–52.

    PubMed  CAS  Google Scholar 

  98. O’Reilly T, McSheehy PM, Wenger F, et al. Patupilone (epothilone B, EPO906) inhibits growth and metastasis of experimental prostate tumors in vivo. Prostate 2005;65:231–40.

    PubMed  Google Scholar 

  99. Altmann KH. Recent developments in the chemical biology of epothilones. Curr Pharm Des 2005;11:1595–613.

    PubMed  CAS  Google Scholar 

  100. 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.

    PubMed  CAS  Google Scholar 

  101. Wartmann M, Altmann KH. The biology and medicinal chemistry of epothilones. Curr Med Chem Anticancer Agents 2002;2:123–48.

    PubMed  CAS  Google Scholar 

  102. Calvert PM, O’Neill V, Twelves C, et al. A phase I clinical and pharmacokinetic study of EPO906 (Epothilone B), given every three weeks, in patients with advanced solid tumors. Proc Am Soc Clin Oncol 2001;20:A429.

    Google Scholar 

  103. Rubin EH, Rothermel J, Fisseha T, et al. Phase I dose-finding study of weekly single-agent patupilone in patients with advanced solid tumors. J Clin Oncol 2005;23:9120–9.

    PubMed  CAS  Google Scholar 

  104. Gadgeel SM, Wozniak A, Boinpally RR, et al. Phase I clinical trial of BMS-247550, a derivative of epothilone B, using accelerated titration 2B design. Clin Cancer Res 2005;11:6233–9.

    PubMed  CAS  Google Scholar 

  105. Aghajanian C, Burris HA, Jones S, et al. Phase I study of the novel epothilone analog Ixabepilone (BMS-247550) in patients with advanced solid tumors and lymphomas. J Clin Oncol 2007;25:1082–8.

    PubMed  CAS  Google Scholar 

  106. Hussain M, Tangen CM, Lara Jr PN, et al. Ixabepilone (epothilone B analogue BMS-247550) is active in chemotherapy-naïve patients with hormone-refractory prostate cancer: a Southwest Oncology Group trial S0111. J Clin Oncol 2005;23:8724–9.

    PubMed  Google Scholar 

  107. Galsky MD, Small EJ, Oh WK, et al. Multi-institutional randomized phase II trial of the epothilone B analog ixabepilone (BMS-247550) with or without estramustine phosphate in patients with progressive castrate metastatic prostate cancer. J Clin Oncol 2005;23:1439–46.

    PubMed  CAS  Google Scholar 

  108. Rosenberg JE, Weinberg VK, Kelly WK, et al. Activity of second-line chemotherapy in docetaxel-refractory hormone refractory prostate cancer patients. Randomized phase 2 study of ixabepilone or mitoxantrone and prednisone. Cancer 2007;110(3):556–63.

    PubMed  CAS  Google Scholar 

  109. Wilding G, Chen Y, DiPaola RP, et al. E3803: updated results on phase II study of a weekly schedule of BMS-247550 for patients with castrate refractory prostate cancer (CRPC). J Clin Oncol 2008;26(Suppl):A5070.

    Google Scholar 

  110. Chi KN, Beardsley EK, Venner PM, et al. A phase II study of patupilone in patients with metastatic hormone refractory prostate cancer (HRPC) who have progressed after docetaxel. J Clin Oncol 2008;26(15S) May 20 Suppl:516.

    Google Scholar 

  111. Hussain A, DiPaola RS, Baron AD, et al. Phase II trial of weekly patupilone in patients with castration-resistant prostate cancer. Ann Oncol 2009;20:492–7.

    PubMed  CAS  Google Scholar 

  112. Smaletz O, Galsky M, Scher HI, et al. Pilot study of epothilone B analog (BMS-247550) and estramustine phosphate in patients with progressive metastatic prostate cancer following castration. Ann Oncol 2003;14:1518–24.

    PubMed  CAS  Google Scholar 

  113. Beer TM, Higano CS, Saleh M, et al. Phase II study of KOS-862 in patients with metastatic androgen independent prostate cancer previously treated with docetaxel. Invest New Drugs 2007;25:565–70.

    PubMed  CAS  Google Scholar 

  114. Sanofi-aventis. XRP6258 investigator’s brochure. Antony (France): Sanofi-aventis; 2000.

    Google Scholar 

  115. Mita AC, Denis LJ, Rowinsky EK, et al. Phase I and pharmacokinetic study of XRP6258 (RPR 116258A), a novel taxane administered as a 10 hour infusion every 3 weeks in patients with advanced solid tumors. Clin Cancer Res 2009;15(2):723–30.

    PubMed  CAS  Google Scholar 

  116. Pivot X, Koralewski P, Hidalgo JL, et al. A multicenter phase II study of XRP6528 administered as a 1-h i.v. infusion every 3 weeks in taxane-resistant metastatic breast cancer patients. Ann Oncol 2008;19(9):1547–52.

    PubMed  CAS  Google Scholar 

  117. De Bono JS, Oudard S, Ozguroglu M, et al. Cabazitaxel or mitosantrone with presdnisone in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel: Final results of a multinational phase III trial (TROPIC). ASCO Annual Meeting Proceedings. J Clin Oncol 2010;28:4508.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Experimental Therapeutics Section, Medical Oncology Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA

    Antonio Tito Fojo

Authors
  1. Antonio Tito Fojo
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David E. Adelberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antonio Tito Fojo .

Editor information

Editors and Affiliations

  1. Medical Oncology Branch, NIH National Cancer Institute, Rockville Pike 9000, Bethesda, 20892, Maryland, USA

    William D. Figg

  2. Medical Oncology Branch, NIH National Cancer Institute, Rockville Pike 9000, Bethesda, 20892, Maryland, USA

    Cindy H. Chau

  3. School of Medicine, Dept. Urology, University of California, San Francisco, Divisadero Street 1600, San Francisco, 94115, California, USA

    Eric J. Small

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Fojo, A.T., Adelberg, D.E. (2010). Microtubule Targeting Agents. In: Figg, W., Chau, C., Small, E. (eds) Drug Management of Prostate Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-60327-829-4_16

Download citation

  • DOI: https://doi.org/10.1007/978-1-60327-829-4_16

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-60327-831-7

  • Online ISBN: 978-1-60327-829-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation