Advertisement

Circumvention of Biologic Diversity of Cancer Metastasis

  • Isaiah J. Fidler

Abstract

The major challenge facing the oncologist is how to treat cancer that has disseminated to and is growing in multiple organs throughout the body. Despite major advances in general patient care, surgical techniques, and adjuvant therapies, most deaths from cancer are caused by the growth of metastases that are resistant to chemotherapy or radiotherapy. A major factor which prevents treatment of metastases is the fact that cancer cells populating both primary and secondary neoplasms are biologically heterogeneous (1, 2). By the time of diagnosis, and certainly in clinically advanced lesions, malignant neoplasms contain multiple cell populations exhibiting a wide range of biological characteristics such as cell surface structures, growth rate, sensitivity to various cytotoxic drugs, and the ability to further invade and metastasize. The implication of the heterogeneous responses of tumor cells to conventional anticancer drugs is that the successful therapy of disseminated metastases must circumvent the problems of biologic heterogeneity and be a treatment modality to which resistance is unlikely to develop.

Keywords

Alveolar Macrophage Spontaneous Metastasis Muramyl Dipeptide Human Blood Monocyte Conventional Anticancer Drug 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    I. J. Fidler and I. R. Hart, Biological diversity in metastatic neoplasms: Origins and implications. Science, 217, 998–1003 (1982).PubMedCrossRefGoogle Scholar
  2. 2.
    I. J. Fidler and G. Poste, The cellular heterogeneity of malignant neoplasms: Implications for adjuvant chemotherapy. Semin. Oncol. 12, 207–222 (1985).PubMedGoogle Scholar
  3. 3.
    I. J. Fidler, Macrophages and metastases: A biological approach to cancer therapy. Cancer Res. 45, 4714–4726 (1985).PubMedGoogle Scholar
  4. 4.
    L. Chedid, L. Carelli, and F. Audibert, Recent developments concerning muramyl dipeptide, a synthetic immunoregulating molecule. J. Reticuloendothel. Soc. 26, 631–641 (1979).PubMedGoogle Scholar
  5. 5.
    E. Lederer, Synthetic immunostimulants derived from the bacterial cell wall. J. Med. Chem. 23, 819–825 (1980).PubMedCrossRefGoogle Scholar
  6. 6.
    W. E. Fogler and I. J. Fidler, Modulation of the immune response by muramyl dipeptide. In: Immune Modulation Agents and Their Mechanisms (M. A. Chirigos and R. L. Fenichel, Eds.), pp. 499–512. Marcel Dekker, New York, 1984.Google Scholar
  7. 7.
    I. J. Fidler, The MAF dilemma. Lymphokine Res. 3, 51–54 (1984).PubMedGoogle Scholar
  8. 8.
    I. Saiki and I. J. Fidler, Synergistic activation by recombinant mouse interferon-gamma and muramyl dipeptide of tumoricidal properties in mouse macrophages. J. Immunol. 135, 684–688, (1985).PubMedGoogle Scholar
  9. 9.
    I. Saiki, S. Sone, W. E. Fogler, E. S. Kleinerman, G. Lopez-Berestein, and I. J. Fidler, Synergism between human recombinant gamma-interferon and muramyl dipeptide encapsulated in liposomes for activation of antitumor properties in human blood monocytes. Cancer Res. 45, 6188–6193, (1985).PubMedGoogle Scholar
  10. 10.
    I. J. Fidler, W. E. Fogler, E. S. Kleinerman, and I. Saiki, Abrogation of species specificity for activation of tumoricidal properties in macrophages by recombinant mouse or human gamma interferon encapsulated in liposomes. J. Immunol. 135, 4289–4294, (1985).PubMedGoogle Scholar
  11. 11.
    J. B. Jr. Hibbs. Discrimination between neoplastic and nonneoplastic cells in vitro by activated macrophages. J. Natl. Cancer Inst. 53, 1487–1492, (1974).PubMedGoogle Scholar
  12. 12.
    C. D. Bucana, L. C. Hoyer, A. J. Schroit, E. S. Kleinerman, and I. J. Fidler, Ultrastructural studies of the interaction between liposomes-activated human blood monocytes and allogeneic tumor cells in vitro. Am. J. Pathol. 112, 101–111, (1983).PubMedGoogle Scholar
  13. 13.
    I. J. Fidler, Recognition and destruction of target cells by tumoricidal macrophages. Isr. J. Med. Sci. 14, 177–191, (1978).PubMedGoogle Scholar
  14. 14.
    I. J. Fidler and E. S. Kleinerman, Lymphokine-activated human blood monocytes destroy tumor cells but not normal cells under cocultivation conditions. J. Clin. Oncol. 2, 937–943, (1984).PubMedGoogle Scholar
  15. 15.
    W. E. Fogler and I. J. Fidler, Nonselective destruction,of murine neoplastic cells by syngeneic tumoricidal macrophages. Cancer Res. 45, 14–18, (1985).PubMedGoogle Scholar
  16. 16.
    G. Poste, R. Kirsh, W. Fogler, and I. J. Fidler, J. Activation of tumoricidal properties in mouse macrophages by lymphokines encapsulated in liposomes. Cancer Res. 39, 881–892, (1979).PubMedGoogle Scholar
  17. 17.
    G. Poste and R. Kirsh, Rapid decay of tumoricidal activity and loss of responsiveness to lymphokines in inflammatory macrophages. Cancer Res. 39, 2582–2590, (1979).PubMedGoogle Scholar
  18. 18.
    G. Poste, The tumoridal properties of inflammatory tissue microphages and multinucleate giant cells. Am. J. Pathol. 96, 595–606, (1979).PubMedGoogle Scholar
  19. 19.
    A. C. Allison, Mode of action of immunological adjuvants. J. Reticuloendothel. Soc. 26, 619–630, (1979).PubMedGoogle Scholar
  20. 20.
    A. J. Schroit and I. J. Fidler, Effects of liposome structure and lipid composition on the activation of the tumoricidal properties of macrophages by liposomes containing muramyl dipeptide. Cancer Res. 42, 161–167, (1982).PubMedGoogle Scholar
  21. 21.
    G. Poste, R. Kirsh, and P. Bugelski, Liposomes as a drug delivery system in cancer therapy. In: Novel Approaches to Cancer Chemotherapy (P. S. Sunkara, Ed.), pp. 166–221. Academic Press, New York, 1984.Google Scholar
  22. 22.
    A. J. Schroit, I. R. Hart, J. Madsen, and I. J. Fidler, Selective delivery of drugs encapsulated in liposomes: Natural targeting to macrophages involved in various disease states. J. Biol. Response Modif. 2, 97–100, (1983).Google Scholar
  23. 23.
    I. J. Fidler, Therapy of spontaneous metastases by intravenous injection of liposomes containing lymphokines. Science, 208, 1469–1471, (1980).PubMedCrossRefGoogle Scholar
  24. 24.
    I. J. Fidler, S. Sone, W. E. Fogler, and Z. L. Barnes, Eradication of spontaneous metastases and activation of alveolor macrophages by intravenous injection of liposomes containing muramyl dipeptide. Proc. Natl. Acad. Sci. U.S.A. 78, 1680–1684, (1981).PubMedCrossRefGoogle Scholar
  25. 25.
    S. D. Deodhar, B. P. Barna, M. Edinger, and T. Chiang, Inhibition of lung metastases by liposomal immunotherapy in a murine fibrosarcoma model. J. Biol. Response Modif. 1, 27–34, (1982).Google Scholar
  26. 26.
    G. Lopez-Berestein, L. Milas, N. Hunter, K. Mehta, D. Eppstein, M. A. VanderPas, T. R. Mathews, and E. M. Hersh, Prophylaxis and treatment with liposome-encapsulated 6-O-steroyl-N-acetyl muramyl-L-aminobutyryl-D-isoglutamine. Clin. Exp. Metastasis, 2, 366–367, (1984).Google Scholar
  27. 27.
    N. C. Phillips, M. L. Mora, L. Chedid, P. Lefrancier, and J. M. Bernard, Activation of tumoricidal activity and eradication of experimental metastases by freeze-dried liposomes containing a new lipophilic muramyl derivative. Cancer Res. 45, 128–134, (1985).PubMedGoogle Scholar
  28. 28.
    D. A. Eppstein, M. A. Van Der Pas, E. B. Fraser-Smith, C. G. Kurahara, P. L. Feigner, T. R. Matthews, R. V. Waters, M. C. Venuti, G. H. Jones, R. Metha, G. Lopez-Berestein, Liposome-encapsulated muramyl dipeptide analogue enhances non-specific host immunity. Int. J. Immunother. 2, 115–126, (1986).Google Scholar
  29. 29.
    J. E. Talmadge, B. F. Lenz, R. Klabansky, R. Simon, C. Riggs, S. Guo, R. K. Oldham, and I. J. Fidler, Therapy of autochthonous skin cancers in mice with intravenously injected liposomes containing muramyltripeptide. Cancer Res. 46, 1160–1163, (1986).PubMedGoogle Scholar
  30. 30.
    S. Sone and I. J. Fidler, Synergistic activation by lymphokines and muramyl dipeptide of tumoricidal properties in rat alveolar macrophages. J. Immunol. 125, 2454–2460, (1980).PubMedGoogle Scholar
  31. 31.
    I. J. Fidler and A. J. Schroit, Synergism between lymphokines and muramyl dipeptide encapsulated in liposomes: In situ activation of macrophages and therapy of spontaneous cancer metastasis. J. Immunol. 133, 515–518, (1984).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Isaiah J. Fidler
    • 1
  1. 1.Department of Cell Biology-173The University of Texas, M. D. Anderson Hospital and Tumor InstituteHoustonUSA

Personalised recommendations