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Strategies for the Development of Novel Taxol-Like Agents

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Microtubule Protocols

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 137))

Abstract

Taxol, the first microtubule stabilizer identified, is one of the most important new anticancer drugs to be brought to the clinic in the past 20 yr. The clinical success of Taxol? led to the development of a second-generation taxane, docetaxel (Taxotere™), and multiple third-generation taxane derivatives are under development. Non-taxane microtubule-stabilizers of diverse chemical structures, including the epothilones and discodermolide, show promising preclinical activities and several epothilones are progressing through clinical trials. One important advantage of the new stabilizers is their ability to circumvent drug resistance mechanisms. The clinical development of these new classes of agents suggests that microtubule stabilizers will continue to be important drugs for the treatment of cancer. This chapter provides a brief history of Taxol and the discovery and development status of other classes of microtubule stabilizers. Although all microtubule-stabilizers share similar mechanisms of action, interesting subtle differences among the stabilizers are being detected. This chapter also provides some strategies for identifying the differences among microtubule stabilizers that may help prioritize them for development and clinical use.

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References

  1. Rowinsky, E. K. and Tolcher, A. W. (2001) Antimicrotubule agents, in Cancer Principles and Practice of Oncology, Vol. 1, (DeVita, V. T. J., Hellman, S., and Rosenberg, S. A., eds.), Lippincott, Williams and Wilkins, Philadelphia, PA, pp. 431–447.

    Google Scholar 

  2. Pegram, M. D., Konecny, G. E., O’Callaghan, C., Beryt, M., Pietras, R., and Slamon, D. J. (2004) Rational combinations of trastuzumab with chemotherapeutic drugs used in the treatment of breast cancer. J. Natl. Cancer Inst. 96, 739–749.

    Article  CAS  PubMed  Google Scholar 

  3. Wani, M. C., Taylor, H. L., Wall, M. E., Coggon, P., and McPhail, A. T. (1971) Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. J. Am. Chem. Soc. 93, 2325–2327.

    Article  CAS  PubMed  Google Scholar 

  4. Wall, M. E. and Wani, M. C. (1995) Camptothecin and taxol: discovery to clinic—thirteenth Bruce F. Cain Memorial Award Lecture. Cancer Res. 55, 753–760.

    CAS  PubMed  Google Scholar 

  5. Schiff, P. B., Fant, J., and Horwitz, S. B. (1979) Promotion of microtubule assembly in vitro by taxol. Nature 277, 665–667.

    Article  CAS  PubMed  Google Scholar 

  6. Schiff, P. B. and Horwitz, S. B. (1980) Taxol stabilizes microtubules in mouse fibroblast cells. Proc. Natl. Acad. Sci. USA 77, 1561–1565.

    Article  CAS  PubMed  Google Scholar 

  7. Crown, J., O’Leary, M., and Ooi, W. S. (2004) Docetaxel and paclitaxel in the treatment of breast cancer: a review of clinical experience. Oncologist 9, 24–32.

    Article  CAS  PubMed  Google Scholar 

  8. Camps, C., Felip, E., Sanchez, J. M., et al. (2005) Phase II trial of the novel taxane BMS-184476 as second-line in non-small-cell lung cancer. Ann. Oncol. 16, 597–601.

    Article  CAS  PubMed  Google Scholar 

  9. Bollag, D. M., McQueney, P. A., Zhu, J., et al. (1995) Epothilones, a new class of microtubule-stabilizing agents with a taxol-like mechanism of action. Cancer Res. 55, 2325–2333.

    CAS  PubMed  Google Scholar 

  10. Bode, C. J., Gupta, M. L., Jr., Reiff, E. A., Suprenant, K. A., Georg, G. I., and Himes, R. H. (2002) Epothilone and paclitaxel: unexpected differences in promoting the assembly and stabilization of yeast microtubules. Biochemistry 41, 3870–3874.

    Article  CAS  PubMed  Google Scholar 

  11. Kowalski, R. J., Giannakakou, P., and Hamel, E. (1997) Activities of the microtubule-stabilizing agents epothilones A and B with purified tubulin and in cells resistant to paclitaxel (Taxol™). J. Biol. Chem. 272, 2534–2541.

    Article  CAS  PubMed  Google Scholar 

  12. Goodin, S., Kane, M. P., and Rubin, E. H. (2004) Epothilones: mechanism of action and biologic activity. J. Clin. Oncol. 22, 2015–2025.

    Article  CAS  PubMed  Google Scholar 

  13. Chou, T. C., Dong, H., Zhang, X., Tong, W. P., and Danishefsky, S. J. (2005) Therapeutic cure against human tumor xenografts in nude mice by a microtubule stabilization agent, fludelone, via parenteral or oral route. Cancer Res. 65, 9445–9454.

    Article  CAS  PubMed  Google Scholar 

  14. Low, J. A., Wedam, S. B., Lee, J. J., et al. (2005) Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in metastatic and locally advanced breast cancer. J. Clin. Oncol. 23, 2726–2734.

    Article  CAS  PubMed  Google Scholar 

  15. Galsky, M. D., Small, E. J., Oh, W. K., et al. (2005) 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. 23, 1439–1446.

    Article  CAS  PubMed  Google Scholar 

  16. de Jonge, M. and Verweij, J. (2005) The epothilone dilemma. J. Clin. Oncol. 23, 9048–9050.

    Article  PubMed  Google Scholar 

  17. ter Haar, E., Kowalski, R. J., Hamel, E., et al. (1996) Discodermolide, a cytotoxic marine agent that stabilizes microtubules more potently than taxol. Biochemistry 35, 243–250.

    Article  PubMed  Google Scholar 

  18. Long, B., Carboni, J., Wasserman, A., et al. (1998) Eleutherobin, a novel cytotoxic agent that induces tubulin polymerization, is similar to paclitaxel (Taxol). Cancer Res. 58, 1111–1115.

    CAS  PubMed  Google Scholar 

  19. Hamel, E., Sackett, D. L., Vourloumis, D., and Nicolaou, K. C. (1999) The coralderived 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 38, 5490–5498.

    Article  CAS  PubMed  Google Scholar 

  20. Mooberry, S. L., Tien, G., Hernandez, A. H., Plubrukarn, A., and Davidson, B. S. (1999) Laulimalide and isolaulimalide, new paclitaxel-like microtubule-stabilizing agents. Cancer Res. 59, 653–660.

    CAS  PubMed  Google Scholar 

  21. Hood, K. A., West, L. M., Rouwe, B., et al. (2002) Peloruside A, a novel antimitotic agent with paclitaxel-like microtubule-stabilizing activity. Cancer Res. 62, 3356–3360.

    CAS  PubMed  Google Scholar 

  22. Isbrucker, R. A., Cummins, J., Pomponi, S. A., Longley, R. E., and Wright, A. E. (2003) Tubulin polymerizing activity of dictyostatin-1, a polyketide of marine sponge origin. Biochem. Pharmacol. 66, 75–82.

    Article  CAS  PubMed  Google Scholar 

  23. Kowalski, R. J., Giannakakou, P., Gunasekera, S. P., Longley, R. E., Day, B. W., and Hamel, E. (1997) 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. 52, 613–622.

    CAS  PubMed  Google Scholar 

  24. Honore, S., Kamath, K., Braguer, D., Wilson, L., Briand, C., and Jordan, M. A. (2003) Suppression of microtubule dynamics by discodermolide by a novel mechanism is associated with mitotic arrest and inhibition of tumor cell proliferation. Mol. Cancer Ther. 2, 1303–1311.

    CAS  PubMed  Google Scholar 

  25. Martello, L. A., McDaid, H. M., Regl, D. L., et al. (2000) Taxol and discodermolide represent a synergistic drug combination in human carcinoma cell lines. Clin. Cancer Res. 6, 1978–1987.

    CAS  PubMed  Google Scholar 

  26. Honore, S., Kamath, K., Braguer, D., et al. (2004) Synergistic suppression of microtubule dynamics by discodermolide and paclitaxel in non-small cell lung carcinoma cells. Cancer Res. 64, 4957–4964.

    Article  CAS  PubMed  Google Scholar 

  27. Mita, A., Lockhart, A., Chen, T.-L., et al. (2004) A phase I pharmacokinetic (PK) trial of XAA296A (discodermolide) administered every 3 wks to adult patients with advanced solid malignancies. J. Clin. Oncol. 22, 2025.

    Google Scholar 

  28. Pryor, D. E., O’Brate, A., Bilcer, G., et al. (2002) 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 41, 9109–9115.

    Article  CAS  PubMed  Google Scholar 

  29. Mooberry, S. L., Randall-Hlubek, D. A., Leal, R. M., et al. (2004) Microtubule-stabilizing agents based on designed laulimalide analogues. Proc. Natl. Acad. Sci. USA 101, 8803–8808.

    Article  CAS  PubMed  Google Scholar 

  30. Gaitanos, T. N., Buey, R. M., Diaz, J. F., et al. (2004) Peloruside A does not bind to the taxoid site on beta-tubulin and retains its activity in multidrug-resistant cell lines. Cancer Res. 64, 5063–5067.

    Article  CAS  PubMed  Google Scholar 

  31. Madiraju, C., Edler, M. C., Hamel, E., et al. (2005) Tubulin assembly, taxoid site binding, and cellular effects of the microtubule-stabilizing agent dictyostatin. Biochemistry 44, 15,053–15,063.

    Article  CAS  PubMed  Google Scholar 

  32. Tinley, T. L., Randall-Hlubek, D. A., Leal, R. M., et al. (2003) Taccalonolides E and A: plant-derived steroids with microtubule-stabilizing activity. Cancer Res. 63, 3211–3220.

    CAS  PubMed  Google Scholar 

  33. Edler, M. C., Buey, R. M., Gussio, R., et al. (2005) Cyclostreptin (FR182877), an antitumor tubulin-polymerizing agent deficient in enhancing tubulin assembly despite its high affinity for the taxoid site. Biochemistry 44, 11,525–11,538.

    Article  PubMed  Google Scholar 

  34. Buey, R. M., Barasoain, I., Jackson, E., et al. (2005) Microtubule interactions with chemically diverse stabilizing agents: thermodynamics of binding to the Paclitaxel site predicts cytotoxicity. Chem. Biol. 12, 1269–1279.

    Article  CAS  PubMed  Google Scholar 

  35. Cabral, F. (2001) Factors determining cellular mechanisms of resistance to antimitotic drugs. Drug Resist. Updat. 4, 3–8.

    Article  CAS  PubMed  Google Scholar 

  36. Orr, G. A., Verdier-Pinard, P., McDaid, H., and Horwitz, S. B. (2003) Mechanisms of Taxol resistance related to microtubules. Oncogene 22, 7280–7295.

    Article  CAS  PubMed  Google Scholar 

  37. Gazitt, Y., Rothenberg, M. L., Hilsenbeck, S. G., Fey, V., Thomas, C., and Montegomrey, W. (1998) Bcl-2 overexpression is associated with resistance to paclitaxel, but not gemcitabine, in multiple myeloma cells. Int. J. Oncol. 13, 839–848.

    CAS  PubMed  Google Scholar 

  38. Buchholz, T. A., Davis, D. W., McConkey, D. J., et al. (2003) Chemotherapy-induced apoptosis and Bcl-2 levels correlate with breast cancer response to chemotherapy. Cancer J. 9, 33–41.

    Article  CAS  PubMed  Google Scholar 

  39. Zhou, J., O’Brate, A., Zelnak, A., and Giannakakou, P. (2004) Survivin deregulation in beta-tubulin mutant ovarian cancer cells underlies their compromised mitotic response to taxol. Cancer Res. 64, 8708–8714.

    Article  CAS  PubMed  Google Scholar 

  40. Lee, J. J. and Swain, S. M. (2005) Development of novel chemotherapeutic agents to evade the mechanisms of multidrug resistance (MDR). Semin. Oncol. 32, S22–S26.

    Article  CAS  PubMed  Google Scholar 

  41. Borst, P. and Elferink, R. O. (2002) Mammalian ABC transporters in health and disease. Annu. Rev. Biochem. 71, 537–592.

    Article  CAS  PubMed  Google Scholar 

  42. Chiou, J. F., Liang, J. A., Hsu, W. H., Wang, J. J., Ho, S. T., and Kao, A. (2003) Comparing the relationship of Taxol-based chemotherapy response with P-glycoprotein and lung resistance-related protein expression in non-small cell lung cancer. Lung 181, 267–273.

    Article  CAS  PubMed  Google Scholar 

  43. Penson, R. T., Oliva, E., Skates, S. J., et al. (2004) Expression of multidrug resistance-1 protein inversely correlates with paclitaxel response and survival in ovarian cancer patients: a study in serial samples. Gynecol. Oncol. 93, 98–106.

    Article  CAS  PubMed  Google Scholar 

  44. Yeh, J. J., Hsu, W. H., Wang, J. J., Ho, S. T., and Kao, A. (2003) Predicting chemotherapy response to paclitaxel-based therapy in advanced non-small-cell lung cancer with P-glycoprotein expression. Respiration 70, 32–35.

    Article  CAS  PubMed  Google Scholar 

  45. Chou, T. C., Zhang, X. G., Harris, C. R., et al. (1998) Desoxyepothilone B is curative against human tumor xenografts that are refractory to paclitaxel. Proc. Natl. Acad. Sci. USA 95, 15,798–15,802.

    Article  CAS  PubMed  Google Scholar 

  46. Hofstetter, B., Vuong, V., Broggini-Tenzer, A., et al. (2005) Patupilone acts as radiosensitizing agent in multidrug-resistant cancer cells in vitro and in vivo. Clin. Cancer Res. 11, 1588–1596.

    Article  CAS  PubMed  Google Scholar 

  47. Lee, F. Y., Borzilleri, R., Fairchild, C. R., et al. (2001) BMS-247550: a novel epothilone analog with a mode of action similar to paclitaxel but possessing superior antitumor efficacy. Clin. Cancer Res. 7, 1429–1437.

    CAS  PubMed  Google Scholar 

  48. Eng, C., Kindler, H. L., Nattam, S., et al. (2004) A phase II trial of the epothilone B analog, BMS-247550, in patients with previously treated advanced colorectal cancer. Ann. Oncol. 15, 928–932.

    Article  CAS  PubMed  Google Scholar 

  49. Ross, D. D. and Doyle, L. A. (2004) Mining our ABCs: pharmacogenomic approach for evaluating transporter function in cancer drug resistance. Cancer Cell 6, 105–107.

    Article  CAS  PubMed  Google Scholar 

  50. Fojo, T. and Bates, S. (2003) Strategies for reversing drug resistance. Oncogene 22, 7512–7523.

    Article  CAS  PubMed  Google Scholar 

  51. Hopper-Borge, E., Chen, Z. S., Shchaveleva, I., Belinsky, M. G., and Kruh, G. D. (2004) Analysis of the drug resistance profile of multidrug resistance protein 7 (ABCC10): resistance to docetaxel. Cancer Res. 64, 4927–4930.

    Article  CAS  PubMed  Google Scholar 

  52. Giannakakou, P., Sackett, D. L., Kang, Y. K., et al. (1997) Paclitaxel-resistant human ovarian cancer cells have mutant beta-tubulins that exhibit impaired paclitaxel-driven polymerization. J. Biol. Chem. 272, 17,118–17,125.

    Article  CAS  PubMed  Google Scholar 

  53. Giannakakou, P., Gussio, R., Nogales, E., et al. (2000) A common pharmacophore for epothilone and taxanes: molecular basis for drug resistance conferred by tubulin mutations in human cancer cells. Proc. Natl. Acad. Sci USA 97, 2904–2909.

    Article  CAS  PubMed  Google Scholar 

  54. Gonzalez-Garay, M. L., Chang, L., Blade, K., Menick, D. R., and Cabral, F. (1999) A beta-tubulin leucine cluster involved in microtubule assembly and paclitaxel resistance. J. Biol. Chem. 274, 23,875–23,882.

    Article  CAS  PubMed  Google Scholar 

  55. Schibler, M. J. and Cabral, F. (1986) Taxol-dependent mutants of Chinese hamster ovary cells with alterations in alpha-and beta-tubulin. J. Cell Biol. 102, 1522–1531.

    Article  CAS  PubMed  Google Scholar 

  56. Sale, S., Sung, R., Shen, P., et al. (2002) Conservation of the class I beta-tubulin gene in human populations and lack of mutations in lung cancers and paclitaxel-resistant ovarian cancers. Mol. Cancer Ther. 1, 215–225.

    CAS  PubMed  Google Scholar 

  57. Kelley, M. J., Li, S., and Harpole, D. H. (2001) Genetic analysis of the beta-tubulin gene, TUBB, in non-small-cell lung cancer. J. Natl. Cancer Inst. 93, 1886–1888.

    Article  CAS  PubMed  Google Scholar 

  58. Kohonen-Corish, M. R., Qin, H., Daniel, J. J., et al. (2002) Lack of beta-tubulin gene mutations in early stage lung cancer. Int. J. Cancer 101, 398–399.

    Article  CAS  PubMed  Google Scholar 

  59. Tsurutani, J., Komiya, T., Uejima, H., et al. (2002) Mutational analysis of the beta-tubulin gene in lung cancer. Lung Cancer 35, 11–16.

    Article  PubMed  Google Scholar 

  60. Monzo, M., Rosell, R., Sanchez, J. J., et al. (1999) Paclitaxel resistance in nonsmall-cell lung cancer associated with beta-tubulin gene mutations. J. Clin. Oncol. 17, 1786–1793.

    CAS  PubMed  Google Scholar 

  61. Luduena, R. F. (1998) Multiple forms of tubulin: different gene products and covalent modifications. Int. Rev. Cytol. 178, 207–275.

    Article  CAS  PubMed  Google Scholar 

  62. Kavallaris, M., Kuo, D. Y., Burkhart, C. A., et al. (1997) Taxol-resistant epithelial ovarian tumors are associated with altered expression of specific beta-tubulin isotypes. J. Clin. Invest. 100, 1282–1293.

    Article  CAS  PubMed  Google Scholar 

  63. Hari, M., Yang, H., Zeng, C., Canizales, M., and Cabral, F. (2003) Expression of class III beta-tubulin reduces microtubule assembly and confers resistance to paclitaxel. Cell Motil. Cytoskeleton 56, 45–56.

    Article  CAS  PubMed  Google Scholar 

  64. Lu, Q. and Luduena, R. F. (1993) Removal of beta III isotype enhances taxol induced microtubule assembly. Cell Struct. Funct. 18, 173–182.

    Article  CAS  PubMed  Google Scholar 

  65. Derry, W. B., Wilson, L., Khan, I. A., Luduena, R. F., and Jordan, M. A. (1997) Taxol differentially modulates the dynamics of microtubules assembled from unfractionated and purified beta-tubulin isotypes. Biochemistry 36, 3554–3562.

    Article  CAS  PubMed  Google Scholar 

  66. Kamath, K., Wilson, L., Cabral, F., and Jordan, M. A. (2005) Beta III-tubulin induces paclitaxel resistance in association with reduced effects on microtubule dynamic instability. J. Biol. Chem. 280, 12,902–12,907.

    Article  CAS  PubMed  Google Scholar 

  67. Mozzetti, S., Ferlini, C., Concolino, P., et al. (2005) Class III beta-tubulin overexpression is a prominent mechanism of paclitaxel resistance in ovarian cancer patients. Clin. Cancer Res. 11, 298–305.

    CAS  PubMed  Google Scholar 

  68. Paradiso, A., Mangia, A., Chiriatti, A., et al. (2005) Biomarkers predictive for clinical efficacy of taxol-based chemotherapy in advanced breast cancer. Ann. Oncol. 16, iv14–iv19.

    Article  PubMed  Google Scholar 

  69. Seve, P., Mackey, J., Isaac, S., et al. (2005) Class III beta-tubulin expression in tumor cells predicts response and outcome in patients with non-small cell lung cancer receiving paclitaxel. Mol. Cancer Ther. 4, 2001–2007.

    Article  CAS  PubMed  Google Scholar 

  70. Ferlini, C., Raspaglio, G., Mozzetti, S., et al. (2005) The seco-taxane IDN5390 is able to target class III beta-tubulin and to overcome paclitaxel resistance. Cancer Res. 65, 2397–2405.

    Article  CAS  PubMed  Google Scholar 

  71. Wang, Y., O’Brate, A., Zhou, W., and Giannakakou, P. (2005) Resistance to microtubule-stabilizing drugs involves two events: beta-tubulin mutation in one allele followed by loss of the second allele. Cell Cycle 4, 1847–1853.

    Article  CAS  PubMed  Google Scholar 

  72. Martello, L. A., Verdier-Pinard, P., Shen, H. J., et al. (2003) Elevated levels of microtubule destabilizing factors in a Taxol-resistant/dependent A549 cell line with an alpha-tubulin mutation. Cancer Res. 63, 1207–1213.

    CAS  PubMed  Google Scholar 

  73. He, L., Yang, C. P., and Horwitz, S. B. (2001) Mutations in beta-tubulin map to domains involved in regulation of microtubule stability in epothilone-resistant cell lines. Mol. Cancer Ther. 1, 3–10.

    CAS  PubMed  Google Scholar 

  74. Jordan, M. A. and Wilson, L. (2004) Microtubules as a target for anticancer drugs. Nat. Rev. Cancer 4, 253–265.

    Article  CAS  PubMed  Google Scholar 

  75. Zhou, J. and Giannakakou, P. (2005) Targeting microtubules for cancer chemotherapy. Curr. Med. Chem. Anti-Canc. Agents 5, 65–71.

    Article  CAS  Google Scholar 

  76. Jordan, M. A., Toso, R. J., Thrower, D., and Wilson, L. (1993) Mechanism of mitotic block and inhibition of cell proliferation by taxol at low concentrations. Proc. Natl. Acad. Sci. USA 90, 9552–9556.

    Article  CAS  PubMed  Google Scholar 

  77. Jordan, M. A., Wendell, K., Gardiner, S., Derry, W. B., Copp, H., and Wilson, L. (1996) Mitotic block induced in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death. Cancer Res. 56, 816–825.

    CAS  PubMed  Google Scholar 

  78. Yvon, A. M., Wadsworth, P., and Jordan, M. A. (1999) Taxol suppresses dynamics of individual microtubules in living human tumor cells. Mol. Biol. Cell 10, 947–959.

    CAS  PubMed  Google Scholar 

  79. Tallarida, R. J. (2002) The interaction index: a measure of drug synergism. Pain 98, 163–168.

    Article  CAS  PubMed  Google Scholar 

  80. Tallarida, R. J., Stone, D. J., Jr., and Raffa, R. B. (1997) Efficient designs for studying synergistic drug combinations. Life Sci. 61, PL 417–425.

    Article  Google Scholar 

  81. Grabovsky, Y. and Tallarida, R. J. (2004) Isobolographic analysis for combinations of a full and partial agonist: curved isoboles. J. Pharmacol. Exp. Ther. 310, 981–986.

    Article  CAS  PubMed  Google Scholar 

  82. Chou, T. C. and Talalay, P. (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv. Enzyme Regul. 22, 27–55.

    Article  CAS  PubMed  Google Scholar 

  83. Tallarida, R. J. (2001) Drug synergism: its detection and applications. J. Pharmacol. Exp. Ther. 298, 865–872.

    CAS  PubMed  Google Scholar 

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  1. Southwest Foundation for Biomedical Research, USA

    Susan L. Mooberry PhD

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  1. Susan L. Mooberry PhD
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  1. Nankai University, Tianjin, China

    Jun Zhou

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Mooberry, S.L. (2007). Strategies for the Development of Novel Taxol-Like Agents. In: Zhou, J. (eds) Microtubule Protocols. Methods in Molecular Medicine™, vol 137. Humana Press. https://doi.org/10.1007/978-1-59745-442-1_20

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  • DOI: https://doi.org/10.1007/978-1-59745-442-1_20

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