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Type I Receptor Tyrosine Kinases as Targets for Therapy in Breast Cancer

  • José Baselga
  • John Mendelsohn
Article

Abstract

Breast carcinomas express high levels of type I tyrosine kinase receptors and their ligands. For these reason therapies directed at these receptors have the potential to be useful anti-cancer agents. A series of monoclonal antibodies (MAbs)3 directed against the EGF receptor and the closely related erbB2/HER2/neu receptor are currently under evaluation. These MAbs have shown promising preclinical activity and “chimeric” and “humanized” MAbs have been produced in order to obviate the problem of host immune reactions. These antibodies are currently being tested in clinical trials either alone or in combination with chemotherapeutic agents. Clinical activity with anti-HER2/neu MAbs has been documented in patients with advanced breast cancer. In addition, compounds that inhibit receptor tyrosine kinases have shown significant preclinical activity and are potential candidates for clinical testing.

Tyrosine kinase receptors monoclonal antibodies breast cancer tyrosine kinase inhibitors epidermal growth factor receptor HER2/neu erbB2 

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REFERENCES

  1. 1.
    D. Barnes and G. Sato (1980). Serum-free cell culture: a unifying approach. Cell 22:649–655.Google Scholar
  2. 2.
    S. A. Haronson (1991). Growth Factors and Cancer. Science 254:1146–1153.Google Scholar
  3. 3.
    E. Di Marco, J. H. Pierce, T. P. Fleming, et al., (1989). Autocrine interaction between TGF alpha and the EGF-receptor:quantitative requirements for induction of the malignant phenotype. Oncogene 4:831–838.Google Scholar
  4. 4.
    A. M. Hudziak, J. Schlessinger, and A. Ullrich (1987). Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells. Proc. Natl. Acad. Sci. U.S.A. 84:7159–7163.Google Scholar
  5. 5.
    P. P. Di Fiore, J. H. Pierce, M. H. Kraus, D. Segatto, C. R. King, and S. A. Aaronson (1987). erbB-2 is a potent oncogene when overexpressed in NIH-3T3 cells. Science 237:178–182.Google Scholar
  6. 6.
    M. B. Sporn and G. J. Todaro (1985). Autocrine growth factors and cancer. Nature 313:747–751.Google Scholar
  7. 7.
    T. Kawamoto, J. D. Sato, A. Le, J. Polikoff, G. H. Sato, and J. Mendelsohn (1983). Growth stimulation of A431 cells by EGF: Identification of high affinity receptors for epidermal growth factor by an anti-receptor monoclonal antibody. Proc. Natl. Acad. Sci. U.S.A. 80:1337–1341.Google Scholar
  8. 8.
    G. N. Gill, T. Kawamoto, C. Cochet, et al., (1984). Monoclonal anti-epidermal growth factor receptor antibodies which are inhibitors of epidermal growth factor binding and antagonists of epidermal growth factor-stimulated tyrosine protein kinase activity. J. Biol. Chem. 259:7755–7760.Google Scholar
  9. 9.
    J. D. Sato, T. Kawamoto, A. D. Le, J. Mendelsohn, J. Polikoff, and G. H. Sato (1983). Biological effect in vitro of monoclonal antibodies to human EGF receptors. Mol. Biol. Med. 1:511–529.Google Scholar
  10. 10.
    H. Sunada, B. Magun, J. Mendelsohn, and C. L. MacLeod (1986). Monoclonal antibody against EGF receptor is internalized without stimulating receptor phosphorylation. Proc. Natl. Acad. Sci. U.S.A. 83:3825–3829.Google Scholar
  11. 11.
    H. Sunada, P. Yu, J. S. Peacock, and J. Mendelsohn (1990). Modulation of tyrosine serine and threonine phosphorylation and intracellular processing of the epidermal growth factor receptor by anti-receptor monoclonal antibody. J. Cell Physiol. 142:284–292.Google Scholar
  12. 12.
    T. Kawamoto, J. Mendelsohn, A. Le, G. H. Sato, C. S. Lazar, and G. N. Gill (1984). Relation of epidermal growth factor receptor concentration to growth of human epidermoid carcinoma A431 cells. J. Biol. Chem. 259:7761–7766.Google Scholar
  13. 13.
    C. L. Arteaga, E. Coronado, and C. K. Osborne (1988). Blockade of the epidermal growth factor receptor inhibits transforming growth factor alpha induced but not estrogen-induced growth of hormone-dependent human breast cancer. Mol. Endocrinol. 2:1064–1069.Google Scholar
  14. 14.
    S. E. Bates, N. E. Davidson, E. M. Valverius, et al., (1988). Expression of transforming growth factor-a and its messenger ribonucleic acid in human breast cancer: its regulation by estrogen and its possible functional significance. Mol. Endocrinol. 2:543–555.Google Scholar
  15. 15.
    S. E. Bates, E. M. Valverius, B. W. Ennis, et al., (1990). Expression of TGF-α/EGF receptor pathway in normal human breast epithelial cells. Endocrinol 126:597–607.Google Scholar
  16. 16.
    B. W. Ennis, E. M. Valverius, M. E. Lippman, et al., (1989). Monoclonal anti-EGF receptor antibodies inhibit the growth of malignant and nonmalignant human mammary epithelial cells. Mol. Endocrinol. 3:1830–1838.Google Scholar
  17. 17.
    H. Masui, T. Kawamoto, J. D. Sato, B. Wolf, G. H. Sato, and J. Mendelsohn (1984). Inhibition of human tumor cells in atymic mice by anti-EGF receptor monoclonal antibodies. Cancer Res. 44:1002–1007.Google Scholar
  18. 18.
    J. Mendelsohn (1989). Potential clinical applications of anti-EGF receptor monoclonal antibodies. In M. Furth and M. Greaves, (eds.), Cancer Cells. Cold Spring Harbor Press, New York, pp. 359–362.Google Scholar
  19. 19.
    Z. Fan, H. Masui, I. Altas, and J. Mendelsohn (1993). Blockade of epidermal growth factor receptor function by bivalent and monovalent fragments of 225 anti-epidermal growth factor receptor monoclonal antibodies. Cancer Res. 53:4322–4328.Google Scholar
  20. 20.
    H. Modjtahedi, J. M. Styles, and C. J. Dean (1993). The human EGF receptor as a target for cancer therapy: six new rat mAbs against the receptor on the breast carcinoma MDA-MB 468. Br. J. Cancer 67:247–253.Google Scholar
  21. 21.
    H. Modjtahedi, S. Eccles, G. Box, J. Styles, and C. Dean (1993). Immunotherapy of human tumour xenografts overexpressing the EGF receptor with rat antibodies that block growth factor-receptor interaction. Br. J. Cancer 67:254–261.Google Scholar
  22. 22.
    A. Goldenberg, H. Masui, C. Divgi, H. Kamrath, K. Pentlow, and J. Mendelsohn (1989). EGF receptor expression and localization of nude mouse xenografts using 111Indium labeled anti-EGF receptor monoclonal antibody. J. Natl. Cancer Inst. 81:1616–1625.Google Scholar
  23. 23.
    E. Aboud-Pirak, E. Hurwitz, M. E. Pirak, F. Bellot, J. Schlessinger, and M. Sela (1988). Efficacy of antibodies to epidermal growth factor receptor against KB carcinoma in vitro and in nude mice. J. Natl. Cancer Inst. 80:1605–1611.Google Scholar
  24. 24.
    D. I. Marks and R. M. Fox (1991). DNA damage, poly(ADP-ribosyl)ation and apoptotic cell death as a potential common pathway for cytotoxic drug action. Biochem. Pharmacol. 42:1859–1867.Google Scholar
  25. 25.
    X. Wu, Z. Fan, H. Masui, N. Rosen, and J. Mendelsohn (1995). Apoptosis induced by an anti-epidermal growth factor receptor monoclonal antibody in a human colorectal carcinoma cell line and its delay by insulin. J. Clin. Invest. 95:1897–1905.Google Scholar
  26. 26.
    J. Baselga, L. Norton, H. Masui, et al., (1993). Antitumor effects of doxorubicin in combination with anti-epidermal growth factor receptor monoclonal antibodies. J. Natl. Cancer Inst. 85:1327–1333.Google Scholar
  27. 27.
    J. Baselga, L. Norton, K. Coplan, R. Shalaby, and J. Mendelsohn (1994). Antitumor activity of placitaxel in combination with anti-growth factor receptor monoclonal antibodies in breast cancer xenografts. Proc. Am. Assoc. Cancer Res. (Abstract) 35:2262.Google Scholar
  28. 28.
    C. Divgi, C. Welt, M. Kris, et al., (1991). Phase I and imaging trial of indium-111 labeled anti-EGF receptor monoclonal antibody 225 in patients with squamous cell lung carcinoma. J. Natl. Cancer Inst. 83:97–104.Google Scholar
  29. 29.
    J. Baselga, A. Scott, D. Pfister, et al., (1993). Comparative pharmacology in phase I and imaging trial utilizing anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (MAbs) labeled with 1311 or 111In. Proc. Am. Assoc. Clin. Oncol. (Abstract) 12:368.Google Scholar
  30. 30.
    M. Bos, J. Mendelsohn, D. Bowden, et al., (1996). Phase I Studies of Anti-Epidermal Growth Factor Receptor (EGFR) Chimeric Monoclonal Antibody C225 in Patients with EGFR Overexpressing Tumors. Proc. Am. Soc. Clin. Oncol. (Abstract)Google Scholar
  31. 31.
    U. Rodeck, N. Williams, U. Murthy, and M. Herlyn (1990). Monoclonal antibody 425 inhibits growth stimulation of carcinoma cells by exogenous EGF and tumor-derived EGF/TGF-α. J. Cell. Biochem. 44:69–79.Google Scholar
  32. 32.
    S. Dadparvar, L. Krishna, C. Miyamoto, et al., (1994). Indium-111-labeled anti-EGFr-425 scintigraphy in the detection of malignant gliomas. Cancer 73:884–889.Google Scholar
  33. 33.
    R. Perez-Soler, N. J. Donato, D. M. Shin, et al., (1994). Tumor epidermal growth factor receptor studies in patients with nonsmall-cell lung cancer or head and neck cancer treated with monoclonal antibody RG 83852. J. Clin. Oncol. 12:730–739. Published erratum appears in J. Clin. Oncol. 12(7):1526.Google Scholar
  34. 34.
    M. D. Waterfield, E. L. U. Mayes, P. Stroobant, et al., (1984). A monoclonal antibody to the human epidermal growth factor receptor. J. Cell. Biochem. 20:149–161.Google Scholar
  35. 35.
    H. P. Kalofonos, T. R. Pawlikoska, A. Hemingway, et al., (1989). Antibody guided diagnosis and therapy of brain gliomas using radiolabeled monoclonal antibodies against epidermal growth factor receptor and placental alkaline phosphatase. J. Nucl. Med. 30:1636–1645.Google Scholar
  36. 36.
    J. A. Drebin, U. C. Link, D. F. Stern, R. A. Weinberg, and M. I. Greene (1985). Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. Cell 41:695–706.Google Scholar
  37. 37.
    J. A. Drebin, V. C. Link, R. A. Weinberg, and M. I. Greene (1986). Inhibition of tumor growth by a monoclonal antibody reactive with an oncogene-encoded tumor antigen. Proc. Natl. Acad. Sci. U.S.A. 83:9129–9133.Google Scholar
  38. 38.
    B. M. Fendly, M. Winget, R. M. Hudziak, M. T. Lipari, M. A. Napier, and A. Ullrich (1990). Characterization of murine monoclonal antibodies reactive to either the human epidermal growth factor receptor to HER2/neu gene product. Pepe. 50:1550–1558.Google Scholar
  39. 39.
    R. M. Hudziak, G. D. Lewis, M. Winget, B. M. Fendly, H. M. Shepard, and A. Ullrich (1989). p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor. Mol. Cell. Biol. 9:1165–1172.Google Scholar
  40. 40.
    S. J. McKenzie, P. J. Marks, T. Lam, et al., (1989). Generation and characterization of monoclonal antibodies specific for the human neu oncogene product, p185. Oncogene 4:543–548.Google Scholar
  41. 41.
    I. Stancovski, E. Hurwitz, D. Leitner, A. Ullrich, Y. Yarden, and M. Sela (1991). Mechanistic aspects of the opposing effects of monoclonal antibodies to the erbB-2 receptor on tumor growth. Proc. Natl. Acad. Sci. U.S.A. 88:8691–8695.Google Scholar
  42. 42.
    M. C. Hancock, B. C. Langton, T. Chan, et al., (1991). A monoclonal antibody against the c-erbB-2 protein enhances the cytotoxicity of cis-diamminedichloroplatinum against human breast and ovarian tumor cell lines. Cancer Res. 51:4575–4580.Google Scholar
  43. 43.
    G. D. Lewis, I. Figari, B. Fendly et al., (1993). Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies. Cancer Immunology Immunotherapy 37:255–263.Google Scholar
  44. 44.
    R. J. Pietras, B. M. Fendly, V. R. Chazin, M. D. Pegram, S. D. Howell, and D. J. Slamon (1994). Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast and ovarian cancer cells. Oncogene 9:1829–1838.Google Scholar
  45. 45.
    T. Nishimura, Y. Nakamura, H. Tsukamoto, et al., (1992). Human c-erb B proto-oncogene product as a target for bispecific-antibody-directed adoptive tumor immunotherapy. Int'l. J. Cancer 50:800–804.Google Scholar
  46. 46.
    L. M. Weiner, M. Holmes, G. P. Adams, F. LaCreta, P. Watts, and I. Garcia de Palazzo (1993). A human tumor xenograft model of therapy with a bispecific monoclonal antinody targeting c-erb-B-2 and CD16. Cancer Res. 53:94–100.Google Scholar
  47. 47.
    F. H. Valone, P. A. Kaufman, P. A. Guyre, et al., (1995). Phase Ia/Ib trial of bispecific antibody MDX-210 in patients with advanced breast or ovarian cancer that overexpresses the proto-oncogene HER-2/neu. J. Clin. Oncol. 13:2281–2292.Google Scholar
  48. 48.
    C. M. Weiner, D. Ring, W. Li, et al., (1994). Phase I trial of 2B1, a bispecific murine monoclonal antibody targeting c-erb-2 and CD16. Proc. Am. Soc. Clin. Oncol. (Abstract) 13:978.Google Scholar
  49. 49.
    P. Carter, L. Presta, C. M. Gorman, et al., (1992). Humanization of an anti-p185HER2 antibody for human cancer therapy. Proc. Natl. Acad. Sci. U.S.A. 89:4285–4289.Google Scholar
  50. 50.
    J. Baselga, D. Tripathy, J. Mendelsohn, et al., (1996). Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J. Clin. Oncol. 14:737–744.Google Scholar
  51. 51.
    M. C. Hancock, B. C. Langton, J. Chan, et al., (1991). A monoclonal antibody against the c-erbB-2 protein enhances the cytotoxicity of cis-diamminedichloroplatinum against human breast and ovarian tumor cell lines. Cancer Res. 51:4575–4580.Google Scholar
  52. 52.
    C. L. Arteaga, A. R. Winnier, M. C. Poirier, et al., (1994). p185c-erbB-2 Signaling enhances cisplatin-induced cytotoxicity in human breast carcinoma cells: association between an oncogenic receptor tyrosine kinase and drug-induced DNA repair. Cancer Res. 54:3758–3765.Google Scholar
  53. 53.
    M. Pegram, A. Lipton, R. Pietras, et al., (1995). Phase II study of intravenous recombinant humanized anti-p185 HER-2 monoclonal antibody (rhuMAb HER-2) plus Cisplatin in patients with HER-2/neu overexpressing metastasic breast cancer. Proc. Am. Soc. Clin. Oncol. (Abstract) 1282:7812–7711.Google Scholar
  54. 54.
    A. Levitzki and A. Gazit (1995). Tyrosine kinase inhibition: an approach to drug development. Science 267:1782–1787.Google Scholar
  55. 55.
    N. Osherov, A. Gazit, C. Gilon, A. Levitzki (1993). Selective inhibition of the epidermal growth factor and Her2/Neu receptors by tyrphostins. J. Biol. Chem. 268:11134–11142.Google Scholar
  56. 56.
    D. W. Fry, A. J. Kraker, A. McMichael, et al., (1994). A Specific inhibitor of the epidermal growth factor receptor tyrosine kinase. Science 265:1093–1095.Google Scholar
  57. 57.
    M. Bos, J. Mendelsohn, Y. M. Kim, D. W. Fry, and J. Baselga (1996). A tyrosine kinase inhibitor prevents ligand-induced receptor activation and inhibits growth of cancer cell lines expressing the epidermal growth factor receptor. Proc. Am. Assoc. Cancer Res. (Abstract) 232:768–771.Google Scholar

Copyright information

© Plenum Publishing Corporation 1997

Authors and Affiliations

  • José Baselga
    • 1
  • John Mendelsohn
    • 2
  1. 1.Hospital General Universi+tari Vall D'HebronBarcelonaSpain
  2. 2.The University of Texas M.D. Anderson Cancer CenterHouston

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