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Is there a future for the small molecule in developmental cancer chemotherapy?

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The Search for New Anticancer Drugs

Part of the book series: Cancer Biology and Medicine ((CABM,volume 3))

Abstract

An objective observer tracking the literature relevant to the science of cancer treatment might conclude that all the important questions are now being engendered by advances in molecular biology. Whereas, in the last three decades, mathematicians, physicists and engineers led mankind in an exploration of the solar system, it will, so the molecular biologists argue, be a biology-driven space programme — one targeted at the innermost recesses of the cell itself — which will finally unravel the mysteries of the malignant state. However, even if the new biological revolution generates leaders with the vision of an Einstein or the imagination of an Arthur C. Clarke, it is unlikely that the power of molecular biology alone will give sufficient insights into how the disease might be cured even if it is fully understood.

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References

  1. Lomax, N. R. and Narayanan, V. L. (1988). Chemical Structures of Interest to the Division of Cancer Treatment, Vol. VI. (Bethesda: Drug Synthesis and Chemistry Branch, Developmental Therapeutics Program, National Cancer Institute )

    Google Scholar 

  2. De Pass, J. and Wood-Gush, G. (1990). In Pharmaceutical Industry Perspectives. (London: Barclays de Zoete Wedd)

    Google Scholar 

  3. Tisdale, M. J. (1991). Cancer cachexia. Br. J. Cancer, 63, 337–342

    Article  PubMed  CAS  Google Scholar 

  4. Bibby, M. C., Double, J. A., Ali, S. A., Fearon, K. C. H., Brennan, R. A. and Tisdale M. J. (1987). Characterisation of a transplantable adenocarcinoma of the mouse producing cachexia in recipient animals. J. Natl. Cancer Inst., 78, 539–544

    PubMed  CAS  Google Scholar 

  5. Tisdale, M. J. and Beck, S. A. (10991). Inhibition of tumour-induced lipolysis in vitro and cachexia and tumour growth in vivo by eicosapentaenoic acid. Biochem. Pharmacol., 41,103–107

    Article  PubMed  CAS  Google Scholar 

  6. Smoluk, G. D., Fahey, R. C., Calabro-Jones, P. M., Aguilera, J. A. and Ward, J. F. (1988). Radioprotection of cells in culture by WR-2721 and derivatives: form of the drug responsible for protection. Cancer Res., 48, 3641–3647

    PubMed  CAS  Google Scholar 

  7. Barnes, J. M., Barnes, N. M., Costall, B. and Naylor, R. J. (1991). Development of 5HT3 receptor antagonists as anti-emetics. Pharm. J., 112–114

    Google Scholar 

  8. Brown, R. and Kaye, S. B. (1990). Drug resistance and the problem of treatment failure. In Ponder, B. A. J. and Waring, M. J. (eds.) The Science of Cancer Treatment, pp. 55 - 82. ( Lancaster: Kluwer Academic Publishers )

    Chapter  Google Scholar 

  9. Marx, J. L. (1986). Drug resistance of cancer cells probed. Science, 234, 818–820

    Article  PubMed  CAS  Google Scholar 

  10. Pennock, G. D., Dalton, W. S., Roeske, W. R., Appleton, C. P., Mosley, K., Plezia, P., Miller, T. P. and Salmon, S. E. (1991). Systemic toxic effects associated with high-dose verapamil infusion and chemotherapy administration. J. Natl. Cancer Inst., 83, 105–110

    Article  PubMed  CAS  Google Scholar 

  11. Foster, B. J., Grotzinger, K. R., McKoy, W. M., Rubinstein, L. V. and Hamilton, T. C. (1988). Modulation of induced resistance to adriamycin in two human breast cancer cell lines with tamoxifen or perhexilene maleate. Cancer Chemother. Pharmacol., 22, 147–152

    Article  PubMed  CAS  Google Scholar 

  12. Twentyman, P. R., Fox, N. E. and White, D. J. G. (1987). Cyclosporin A and its analogues as modifiers of adriamycin and vincristine resistance in a multi-drug resistant human lung cancer cell line. Br. J. Cancer, 56, 55–57

    Article  PubMed  CAS  Google Scholar 

  13. Watanabe, Y., Takano, H., Kiue, A., Kohno, K. and Kuwano, M. (1991). Potentiation of etoposide and vincristine by two synthetic 1,4-dihydropyridine derivatives in multidrug-resistant and atypical multidrug-resistant human cancer cells. Anti-cancer Drug Design, 6, 47–58

    PubMed  CAS  Google Scholar 

  14. Pegg, A. E. (1990). Mammalian O6-alkylguanine-DNA alkyltransferase: regulation and importance in response to alkylating carcinogenic and therapeutic agents. Cancer Res., 50, 6119–6129

    PubMed  CAS  Google Scholar 

  15. Yarosh, D. B., Barnes, D. and Erickson, L. C. (1986). Transfection of DNA from a chloroethylnitrosourea-resistant tumour cell line (Mer+) to a sensitive tumour cell line (Mer-) results in a tumour cell line resistant to MNNG and CNU that has increased O6-methylguanine- DNA methyltransferease levels and reduced levels of DNA interstrand crosslinking. Carcinogenesis(London), 7, 1603–1606

    Article  CAS  Google Scholar 

  16. Lee, S. M., Thatcher, N. and Margison, G. P. (1991). O6-Alkylguanine-DNA alkyltransferase depletion and regeneration in human peripheral lymphocytes following dacarbazine and fotemustine. Cancer Res., 51, 619–623

    PubMed  CAS  Google Scholar 

  17. Dolan, M. E., Moschel, R. C. and Pegg, A. E. (1990). Depletion of mammalian O6- alkylguanine-DNA alkyltransferase activity by O6-benzylguanine provides a means to evaluate the role of this protein in protection against carcinogenic and therapeutic alkylating agents. Proc. Natl. Acad. Sci. USA, 5368–5372

    Google Scholar 

  18. Hickman, J. A., Stevens, M. F. G., Gibson, N. W., Langdon, S. P., Fizames, C., Lavelle, F., Atassi, G., Lunt, E. and Tilson, R. M. (1985). Experimental antitumour activity against murine tumor model systems of 8-carbamoyl-3-(2-chloroethyl)imidazo[5,l-d]-l,2,3,5- tetrazin-4(3H)-one (Mitozolomide), a novel broad spectrum agent. Cancer Res., 45, 3008–3013

    PubMed  CAS  Google Scholar 

  19. Newlands, E. S., Blackledge, G., Slack, J. A., Goddard, C., Brindley, C. J., Holden, L. and Stevens, M. F. G. (1985). Phase I clinical trial of mitozolomide. Cancer Treatment Rep. 69, 801–805

    CAS  Google Scholar 

  20. Boyd, M. R. (1989). Status of the NCI preclinical antitumor drug discovery screen. Principles Pract. Oncol., 3, 1–12

    Google Scholar 

  21. Bagshawe, K. D. (1987). Antibody directed enzymes revive anticancer prodrugs concept. Br. J. Cancer, 56, 531–532

    Article  PubMed  CAS  Google Scholar 

  22. Coghlan, A. (1991). A second chance for antibodies. New Scientist, 9th February, 34–39

    Google Scholar 

  23. Robertson, M. (1986). Gene therapy: desperate appliances. Nature (London), 320, 213–214

    Article  CAS  Google Scholar 

  24. Kinnon, C. and Levinsky, R. J. (1990). Gene therapy for cancer. Eur. J. Cancer, 26, 638–640

    Article  PubMed  CAS  Google Scholar 

  25. Wang, C. Y. and Huang, L. (1989). Highly efficient DNA delivery mediated by pH-sensitive immunoliposomes. Biochemistry, 28, 9508–9514

    Article  PubMed  CAS  Google Scholar 

  26. Yang, N.-S., Burkholder, J., Roberts, B., Martinell, B. and McCabe, D. (1990). In vivoand in vitrogene transfer to mammalian somatic cells by particle bombardment. Proc. Natl. Acad. Sci. USA, 87, 9568–9572

    Article  PubMed  CAS  Google Scholar 

  27. Kelly, S. A., Malik, S. and Balkwill, F. R. (1990). Cytokine therapy. In Ponder, B. A. J. and Waring, M. J. (eds.) The Science of Cancer Treatment, pp. 127–159. ( Lancaster: Kluwer Academic Publishers )

    Google Scholar 

  28. Wadler, S. and Schwartz, E. L. (1990). Antineoplastic activity of the combination of interferon and cytotoxic agents against experimental human malignancies: A review. Cancer Res., 50, 3473–3486

    PubMed  CAS  Google Scholar 

  29. Coley, W. B. (1893). The treatment of malignant tumors by repeated innoculations of erysipelas with a report of ten original cases. Am. J. Med. Sci., 105, 487–511

    Article  Google Scholar 

  30. Weisenthal, L. M., Dill, P. L. and Pearson, F. C. (1991). Effect of prior cancer chemotherapy on human tumor-specific cytotoxicity in vitroin response to immunopotentiating biologic response modifiers. J. Natl. Cancer Inst., 83, 37–42

    Article  PubMed  CAS  Google Scholar 

  31. Satoh, M., Inagawa, H., Shimada, Y., Soma, G.-I., Oshima, H. and Mizuno, D. (1987). Endogenous production of tumor necrosis factor in normal mice and human cancer patients by interferons and other cytokines combined with biological response modifiers of bacterial origin. J. Biol. Response Modifiers, 6, 512–514

    CAS  Google Scholar 

  32. Okutomi, T., Inagawa, H., Nishizawa, T., Oshima, H., Soma, G.-I. and Mizuno, D. (1990). Priming effect of orally administered muramyl dipeptide on induction of endogenous tumor necrosis factor. J. Biol. Response Modifiers, 9, 564–569

    CAS  Google Scholar 

  33. Bibby, M.C., Phillips, R.M., Double, J.A. and Pratesi, G. (1991). Anti-tumour activity of flavone acetic acid (NSC-347512) in mice - influence of immune status. Br. J. Cancer, 63, 57–62

    Article  PubMed  CAS  Google Scholar 

  34. Futami, H., Hornung, R. L., Back, T. T., Bull, R., Grays, E. and Wiltrout, R. H. (1990). Systemic alkanization inhibits the ability of flavone acetic acid to augment natural killer activity, induce cytokine gene expression, and synergize with interleukin-2 for the treatment of murine renal cancer. Cancer Res., 50, 7926–7931

    PubMed  CAS  Google Scholar 

  35. Urba, W., Longo, D. L., Lombardo, F. A., and Weiss, R. B. (1988). Enhancement of natural killer activity in human peripheral blood by flavone acetic acid. J. Natl. Cancer Inst., 80, 521–525

    Article  PubMed  CAS  Google Scholar 

  36. Kerr, D. J., Kaye, S. B., Cassidy, J., Bradley, C., Rankin, E. M., Adams, L., Setanoians, A., Young, T., Forrest, G., Soukop, M. and Clavel, M. (1987). Phase I and pharmacokinetic study of flavone acetic acid. Cancer Res., 47, 6776–6781

    PubMed  CAS  Google Scholar 

  37. Mayer, G. D., Krueger, R. F., Betts, R. F., Douglas, R. G., Breinig, M. C. and Morahan, P. S. (1980). In Stringfellow, D. A. (ed.) Interferon and Interferon Inducers: Clinical Applications. (New York: Marcel Dekker, Inc. )

    Google Scholar 

  38. Srikishnan, T. (1990). Structural studies of immunomodulators. Part 2. Crystal structure and conformation of azimexon (BM 12.531) an immunostimulant and an anti-tumor drug. Anti- Cancer Drug Design, 5, 213–220

    Google Scholar 

  39. Larsson, E.-L., Joki, A. and Stålhandski, T. (1987). Mechanism of action of the new immunomodulator LS 2616 on T cell responses. Int. J. Immunopharmacol., 9, 425–431

    Article  PubMed  CAS  Google Scholar 

  40. Kalland, T., Aim, G. and Stålhandski, T. (1985). Augmentation of mouse natural killer cell activity by LS 2616, a new Immunomodulator. J. Immunol., 134, 3956–3961

    PubMed  CAS  Google Scholar 

  41. Li, L. H., Wallace, T. L., Wierenga, W., Stulnick, H. I. and DeKoning, T. F. (1987). Antitumour activity of pyrimidinones, a class of small molecule biological response modifiers. J. Biol. Response Modifiers, 6, 44–55

    Google Scholar 

  42. Scherina, M., Ijzermans, J. N. M., Jeekel, J. and Marquet, R. L. (1990). The antitumour activity of the interferon inducer bropirimine is partially mediated by endogenous tumour necrosis factor α. Cancer Immunol. Immunother., 32, 251–255

    Article  Google Scholar 

  43. Weistenthal, L. M., Dill, P. L. and Pearson, F. C. (1991). Effect of prior cancer chemotherapy on human tumor-specific cytotoxicity in vitroin response to immunopotentiating biologic response modifiers. J. Natl. Cancer Inst., 83, 37–42

    Article  Google Scholar 

  44. Moertel, C. G., Fleming, T. R., MacDonald, J. S., Haller, D. G., Laurie, J. A., Goodman P. J., Ungerleider, J. S., Emerson, W. A., Tormey, D. C., Glick, J. H., Veeder, M. H. and Mailliard, J. A. (1990). Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N. Eng. J. Med., 322, 352–358

    Article  CAS  Google Scholar 

  45. Kalland, T. (1986). Effects of immunomodulator LS 2616 on growth and metastasis of the murine B16-F10 melanoma. Cancer Res., 46, 3018–3022

    PubMed  CAS  Google Scholar 

  46. Vane, J. and Cuatrecasas, P. (1984). Genetic engineering and pharmaceuticals. Nature (London), 312, 303–305

    Article  CAS  Google Scholar 

  47. Wüthrich, K. (1989) Protein structure determination in solution by nuclear magnetic resonance spectroscopy. Science, 243, 45–50

    Article  PubMed  Google Scholar 

  48. Sternberg, M. J. E. and Zvelebil, M. J. J. M. (1990). Prediction of protein structure from sequence. Eur. J. Cancer, 26, 1163–1166

    Article  PubMed  CAS  Google Scholar 

  49. Blundell, T. (1990). Designer drags head for the market place. New Scientist, 9th June, 61–64

    Google Scholar 

  50. Workman, P. (1990). The cell membrane and cell signals: New targets for novel anticancer agents. Ann. Oncol., 1, 100–111

    PubMed  CAS  Google Scholar 

  51. Powis, G., Hickman, J. A., Workman, P., Tritton, T. R., Abita, J. P., Berdel, W. E., Gescher, A., Moses, H. L. and Nicolson, G. L. (1990). The cell membrane and cell signals as targets in cancer chemotherapy. Cancer Res., 50, 2203–2211

    Google Scholar 

  52. Ptashne, M. (1986). Gene regulation by proteins acting nearby and at a distance. Nature (London), 322, 697–701

    Article  CAS  Google Scholar 

  53. Maher, L. J., Wold, B. and Dervan, P. B. (1989). Inhibition of DNA binding proteins by oligonucleotide-directed triple helix formation. Science, 245, 725–730

    Article  PubMed  CAS  Google Scholar 

  54. . Strobel, S. A. and Dervan, P. B. (1991). Single-site enzymatic cleavage of yeast genomic DNA mediated by triple helix formation. Nature (London), 350, 172–174

    Article  CAS  Google Scholar 

  55. Hélène, C. and Toulmé, J.-J. (1990). Specific regulation of gene expression by antisense, sense and antigene nucleic acids. Biochim. Biophys. Acta, 1049, 99–125

    PubMed  Google Scholar 

  56. Stein, C. A. and Cohen, J. S. (1988). Oligonucleotides as inhibitors of gene expression: a review. Cancer Res., 48, 2659–2668

    PubMed  CAS  Google Scholar 

  57. Rothenberg, M., Johnson, G., Laughlin, C., Green, I., Cradock, J., Sarver, N. and Cohen, J. S. (1989). Oligonucleotides as anti-sense inhibitors of gene expression: therapeutic implications. J. Natl. Cancer Inst., 81, 1539–1544

    Article  PubMed  CAS  Google Scholar 

  58. Thurston, D. E. and Thompson, A. S. (1990). The molecular recognition of DNA. Chem. Britain, 26, 767–772

    CAS  Google Scholar 

  59. Clark, A. S., Stevens, M. F. G., Sansom, C. E. and Sehwalbe, C. H. (1990). Anti-tumour imidazotetrazines. Part XXI. Mitozolomide and temozolomide: probes for the major groove of DNA. Anti-Cancer Drug Design, 5, 63–68

    PubMed  CAS  Google Scholar 

  60. Armstrong, R. W., Beau, J. N., Cheon, S. H., Christ, W. J., Fujioka, H., Ham, W. H., Hawkins, L. D., Jin H., Kang, S. H., Kishi, Y., Martinelli, M. J., McWhorter, W. W., Mizuno, M., Nakata, M., Stutz, A. E., Talamas, F. X., Taniguchi, M., Tino, J. A., Ueda, K., Uerishi, J., White, J. B. and Yonaga, M. (1989). Total synthesis of palytoxin carboxylic acid and palytoxin amide. J. Am. Chem. Soc., 111, 7530–7533, and references quoted therein

    Article  CAS  Google Scholar 

  61. Nicolaou, K. C., Skokotas, G., Furuya, S., Suemune, H. and Nicolaou, D. C. (1990). Golfomycin A, a novel designed molecule with DNA-cleaving properties and antitumour activity. Angew. Chem. Int. Ed. Engl., 29, 1064–1068

    Article  Google Scholar 

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Authors
  1. M. F. G. Stevens
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Editors and Affiliations

  1. University of Cambridge, UK

    M. J. Waring (Reader in Chemotherapy) (Reader in Chemotherapy)

  2. CRC Human Cancer Genetics Research Group, Department of Pathology, University of Cambridge, UK

    B. A. J. Ponder (Director) (Director)

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© 1992 Kluwer Academic Publishers

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Stevens, M.F.G. (1992). Is there a future for the small molecule in developmental cancer chemotherapy?. In: Waring, M.J., Ponder, B.A.J. (eds) The Search for New Anticancer Drugs. Cancer Biology and Medicine, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-0385-2_1

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  • DOI: https://doi.org/10.1007/978-94-009-0385-2_1

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-6659-4

  • Online ISBN: 978-94-009-0385-2

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