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Inhibition of the HER-2/neu Oncogene

A Translational Research Model for the Development of Future Targeted Therapies

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Book cover Oncogene-Directed Therapies

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

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Abstract

The HER-2/neu gene encodes a 185-kilodalton (kDa) transmembrane protein that is a member of the type I receptor tyrosine kinase family, whose other members include the epidermal growth factor receptor (EGFR), HER-3, and HER-4 (1). The HER-2/neu receptor protein is expressed in a wide variety of tissues, including the breast, ovary, endometrium, lung, liver, gastrointestinal tract, kidney, and central nervous system, and HER-2/neu is believed to play an important signaling role in cellular proliferation and differentiation in these tissues (2–7).

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References

  1. Rajkumar T, Gullick WJ. The type I growth factor receptors in human breast cancer. Breast Cancer Res Treat 1994; 29: 3–9.

    Article  PubMed  CAS  Google Scholar 

  2. Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL. Human breast cancer: correlation of relapse and survival with amplification on HER-2/neu oncogene. Science 1987; 235: 177–182.

    Article  PubMed  CAS  Google Scholar 

  3. Bigsby RM, Li AX, Bomalaski J, Stehman FB, Look KY, Sutton GP. Immunohistochemical study of HER-2/neu, epidermal growth factor receptor, and steroid receptor expression in normal and malignant endometrium. Obstet Gynecol 1992; 79: 95–100.

    PubMed  CAS  Google Scholar 

  4. Rotter M, Block T, Busch R, Thanner S, Hofier H. Expression of HER-2/neu in renal-cell carcinoma. Correlation with histologic subtypes and differentiation. Int J Cancer 1992; 52: 213–217.

    Article  PubMed  CAS  Google Scholar 

  5. Press MF, Pike MC, Hung G, Zhou JY, Ma Y, George J, et al. Amplification and overexpression of HER-2/neu in carcinomas of the salivary gland: correlation with poor prognosis. Cancer Res 1994; 54: 5675–5682.

    PubMed  CAS  Google Scholar 

  6. Osako T, Miyahara M, Uchino S, Inomata M, Kitano S, Kobayashi M. Immunohistochemical study of c-erbB-2 protein in colorectal cancer and the correlation with patient survival. Oncology 1998; 55: 548–555.

    Article  PubMed  CAS  Google Scholar 

  7. Martin-Lacave I, Utrilla JC. Expression of a neu/c-erbB-2-like product in neuroendocrine cells of mammals. Histol Histopathol 2000; 15: 1027–1033.

    PubMed  CAS  Google Scholar 

  8. Shih C, Padhy LC, Murray M, Weinberg RA. Transforming genes of carcinomas and neuroblastomas introduced into mouse fibroblasts. Nature 1981; 290: 261–264.

    Article  PubMed  CAS  Google Scholar 

  9. Coussens L, Yang-Feng TL, Liao YC, Chen E, Gray A, McGrath J, et al. Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene. Science 1985; 230: 1132–1139.

    Article  PubMed  CAS  Google Scholar 

  10. Semba K, Kamata N, Toyoshima K, Yamamoto T. A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma. Proc Natl Acad Sci USA 1985; 82: 6497–6501.

    Article  PubMed  CAS  Google Scholar 

  11. Bargmann CI, Hung MC, Weinberg RA. The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature 1986; 319: 226–230.

    Article  PubMed  CAS  Google Scholar 

  12. Hung MC, Schechter AL, Chevray PY, Stern DF, Weinberg RA. Molecular cloning of the neu gene: absence of gross structural alteration in oncogenic alleles. Proc Natl Acad Sci USA 1986; 83: 261–264.

    Article  PubMed  CAS  Google Scholar 

  13. Yamamoto T. Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, et al. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature 1986; 319: 230–234.

    Article  PubMed  CAS  Google Scholar 

  14. Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, et al. Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 1989; 244: 707–712.

    Article  PubMed  CAS  Google Scholar 

  15. Berchuck A, Kamel AS, Whitaker R, Kerns B, Olt G, Kinney R, et al. Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res 1990; 50: 4087–4091.

    PubMed  CAS  Google Scholar 

  16. Toikkanen S, Helin H, Isola J, Joensus H. Prognostic significance of HER-2 oncoprotein expression in breast cancer: a 30-year follow-up. J Clin Oncol 1992; 10: 1044–1048.

    PubMed  CAS  Google Scholar 

  17. Seshadri R, Firgaira FA, Horsfall DJ, McCaul K, Setlur V, Kitchen P. Clinical significance of HER2/neu oncogene amplification in primary breast cancer. The South Australian Breast Cancer Study Group. J Clin Oncol 1993; 11: 1936–1942.

    PubMed  CAS  Google Scholar 

  18. Quenel N, Wafflart J, Bonichon F, de Mascarel I, Trojani M, Durand M, et al. The prognostic value of c-erbB2 in primary breast carcinomas: a study on 942 cases. Breast Cancer Res Treat 1995 35: 283–291.

    Article  PubMed  CAS  Google Scholar 

  19. Andrulis IL, Bull SB, Blackstein ME, Sutherland D, Mak C, Sidlofsky S, et al. neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group. J Clin Oncol 1998 16: 1340–1349.

    PubMed  CAS  Google Scholar 

  20. Pauletti G, Dandekar S, Rong H, Ramos L, Peng H, Seshadri R, et al. Assessment of methods for tissue-based detection of the HER-2/neu alteration in human breast cancer: a direct comparison of fluorescence in situ hybridization and immunohistochemistry. J Clin Oncol 2000; 18: 3651–3664.

    PubMed  CAS  Google Scholar 

  21. Press MF, Hung G, Godolphin W, Slamon DJ. Sensitivity of HER-2/neu antibodies in archival tissue samples: potential source of error in immunohistochemical studies of oncogene expression. Cancer Res 1994; 54: 2771–2777.

    PubMed  CAS  Google Scholar 

  22. Pegram MD, Pauletti G, Slamon DJ. HER-2/neu as a predictive marker of response to breast cancer therapy. Breast Cancer Res Treat 1998; 52: 65–77.

    Article  PubMed  CAS  Google Scholar 

  23. Chazin VR, Kaleko M, Miller AD, Slamon DJ. Transformation mediated by the human HER-2 gene independent of the epidermal growth factor receptor. Oncogene 1992; 7: 1859–1866.

    PubMed  CAS  Google Scholar 

  24. Pietras RJ, Fendly B, Chazin VR, Pegram MD, Howell SB, Slamon DJ. Antibody to HER-2/neu receptor blocks DNA repair after cisplatin in human breast and ovarian carcinoma cells. Oncogene 1994; 9: 1829–1838.

    PubMed  CAS  Google Scholar 

  25. Pegram MD, Finn RS, Arzoo K, Beryt M, Pietras RJ, Slamon DJ. The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells. Oncogene 1997; 15: 537–547.

    Article  PubMed  CAS  Google Scholar 

  26. Pegram M, Slamon D. Biological rationale for HER2/neu (c-erbB2) as a target for monoclonal antibody therapy. Semin Oncol 2000; 27: 13–19.

    PubMed  CAS  Google Scholar 

  27. Hudziak RM, Schlessinger J, Ullrich A. Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells. Proc Natl Acad Sci USA 1987; 84: 7159–7163.

    Article  PubMed  CAS  Google Scholar 

  28. Pierce JH, Arnstein P, DiMarco E, Artrip J, Kraus MH, Lonardo F, et al. Oncogenic potential of erbB2 in human mammary epithelial cells. Oncogene 1991; 6: 1189–1194.

    PubMed  CAS  Google Scholar 

  29. Drebin JA, Link VC, Stern DF, Weinberg RA, Greene MI. Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. Cell 1985; 41: 697–706.

    Article  PubMed  CAS  Google Scholar 

  30. Fendly BM, Winget M, Hudziak RM, Lipari MT, Napier MA, Ullrich A. Characterization of murine monoclonal antibodies reactive to either the human epidermal growth factor receptor or HER2/neu gene product. Cancer Res 1990; 50: 1550–1158.

    PubMed  CAS  Google Scholar 

  31. Carter P, Presta L, Gorman CM, Ridgway JB, Henner D, Wong WL, et al. Humanization of an antip185HER2 antibody for human cancer therapy. Proc Natl Acad Sci USA 1992; 89: 4285–4289.

    Article  PubMed  CAS  Google Scholar 

  32. Losman MJ, DeJager RL, Monestier M, Sharkey RM, Goldenberg DM. Human immune response to anti-carcinoembryonic antigen murine monoclonal antibodies. Cancer Res 1990; 50: 1055s - 1058s.

    PubMed  CAS  Google Scholar 

  33. Tjandra JJ, Ramadi L, McKenzie IF. Development of human anti-murine antibody (HAMA) response in patients. Immunol Cell Biol 1990; 68: 367–376.

    Article  PubMed  Google Scholar 

  34. Avner B, Swindell L, Sharp E, Liao SK, Ogden JR, Avner BP, et al. Evaluation and clinical relevance of patient immune responses to intravenous therapy with murine monoclonal antibodies conjugated to adriamycin. Mol Biother 1991; 3: 14–21.

    PubMed  CAS  Google Scholar 

  35. Pietras RJ, Pegram MD, Finn RS, Maneval DA, Slamon DJ. Remission of human breast cancer xenografts on therapy with humanized monoclonal antibody to HER-2 receptor and DNA-reactive drugs. Oncogene 1998; 17: 2235–2249.

    Article  PubMed  CAS  Google Scholar 

  36. Pegram M, Baly D, Wirth C, Gilkerson E, Slamon DJ, Sliwkowski MX. Antibody-dependent cell-mediated cytotoxicity in breast cancer patients in phase III clinical trials of a humanized anti-HER2 antibody. Proc Am Assoc Cancer Res 1997; 38: 602. (Abstr. 4044)

    Google Scholar 

  37. Clynes RA, Towers TL, Presta LG, Ravetch JV. Inhibitory Fc receptors modulate in vivo cytoxicity against tumor targets. Nature Med 2000; 6: 443–446.

    Article  PubMed  CAS  Google Scholar 

  38. Plowman GD, Green JM, Culouscou JM, Carlton GW, Rothwell VM, Buckley S. Heregulin induces tyrosine phosphorylation of HER4/pl80erbB4. Nature 1993; 366: 473–475.

    Article  PubMed  CAS  Google Scholar 

  39. Carraway KL III, Cantley LC. A neu acquaintance for erbB3 and erbB4: a role for receptor heterodimerization in growth signaling. Cell 1994; 78: 5–8.

    Article  PubMed  CAS  Google Scholar 

  40. Sliwkowski MX, Schaefer G, Akita RW, Lofgren JA, Fitzpatrick VD, Nuijens A, et al. Coexpression of erbB2 and erbB3 proteins reconstitutes a high affinity receptor for heregulin. J Biol Chem 1994; 269: 14661–14665.

    Google Scholar 

  41. Klapper LN, Glathe S, Vaisman N, Hynes NE, Andrews GC, Sela M, et al. The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors. Proc Natl Acad Sci USA 1999; 96: 4995–5000.

    Article  PubMed  CAS  Google Scholar 

  42. Reese DM, Slamon DJ. HER-2/neu signal transduction in human breast and ovarian cancer. Stem Cells 1997; 15: 1–8.

    Article  PubMed  CAS  Google Scholar 

  43. Amundadottir LT, Leder P. Signal transduction pathways activated and required for mammary carcinogenesis in response to specific oncogenes. Oncogene 1998; 16: 737–746.

    Article  PubMed  CAS  Google Scholar 

  44. Mansour SJ, Matten WT, Hermann AS, Candia JM, Rong S, Fukasawa K, et al. Transformation of mammalian cells by constitutively active MAP kinase kinase. Science 1994; 265: 966–970.

    Article  PubMed  CAS  Google Scholar 

  45. Landgraf R, Eisenberg D. Heregulin reverses the oligomerization of HER3. Biochemistry 39: 8502–8511.

    Google Scholar 

  46. Pinkas-Kramarski R, Shelly M, Glathe S, Ratzkin BJ, Yarden Y. Neu differentiation factor/neuregulin isoforms activate distinct receptor combinations. J Biol Chem 1996; 271: 19029–19032.

    Article  PubMed  CAS  Google Scholar 

  47. Sliwkowski MX, Lofgren JA, Lewis GD, Hotaling TE, Fendly BM, Fox JA. Nonclinical studies addressing the mechanism of action of trastuzumab (Herceptin). Semin Oncol 1999; 26: 60–70.

    PubMed  CAS  Google Scholar 

  48. Schaefer G, Akita RW, Sliwkowski MX. A discrete three-amino acid segment (LVI) at the C-terminal end of kinase-impaired ErbB3 is required for transactivation of ErbB2. J Biol Chem 1999; 274: 859–866.

    Article  PubMed  CAS  Google Scholar 

  49. Yao R, Cooper GM. Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science 1995; 267: 2003–2006.

    Article  PubMed  CAS  Google Scholar 

  50. Ohmichi M, Decker SJ, Saltiel AR. Activation of phosphatidylinostiol-3 kinase by nerve growth factor involves indirect coupling of the trk proto-oncogene with src homology 2 domains. Neuron 1992; 9: 769–777.

    Article  PubMed  CAS  Google Scholar 

  51. Soltoff SP, Rabin SL, Cantley LC, Kaplan DR. Nerve growth factor promotes the activation of phosphatidylinositol 3-kinase and its association with the trk tyrosine kinase. J Biol Chem 1992; 267: 17472–17477.

    PubMed  CAS  Google Scholar 

  52. Nobes CD, Hawkins P, Stephens L, Hall A. Activation of the small GTP-binding proteins rho and rac by growth factor receptors. J Cell Sci 1995; 108: 225–233.

    PubMed  CAS  Google Scholar 

  53. Stall SP. Molecular cloning of the akt oncogene and its human homologues AKTI an AKT2: amplification of AKT1 in a primary human gastric adenocarcinoma. Proc Natl Acad Sci USA 1987; 84: 5034–5037.

    Article  Google Scholar 

  54. Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three Akts. Genes Dey 1999; 13: 2905–2927.

    Article  CAS  Google Scholar 

  55. Biggs WH III, Meisenhelder J, Hunter T, Cavenee WK, Arden KC. Protein kinase B/Akt-mediated phosphorylation promotes nuclear exclusion of the winged helix transcription factor FKHR1. Proc Natl Acad Sci USA 1999; 96: 7421–7426.

    Article  PubMed  CAS  Google Scholar 

  56. Jackson JG, Kreisberg JI, Koterba AP, Yee D, Brattain MG. Phosphorylation and nuclear exclusion of the forkhead transcription factor FKHR after epidermal growth factor treatment in human breast cancer cells. Oncogene 2000; 19: 4574–4581.

    Article  PubMed  CAS  Google Scholar 

  57. Arboleda J, Lyons JF, Kabbinavar FF, Bray MR, Snow BE, Ayala R, et al. Overexpression of AKT2/PKB(3 leads to upregulation of collagen IV binding receptors, increased invasion and metastasis of human breast and ovarian cancer cells, submitted.

    Google Scholar 

  58. Arboleda J, Slamon DJ. Heregulin induced cell invasion of HER-2/neu transfected breast cancer cell line is mediated through activation of the phosphatidylinositol 3-kinase/AKT2 pathway. Abstract for Cold Spring Harbor Laboratory Meeting on Tyrosine Phosphorylation and Cell Signaling, 1999; p 11.

    Google Scholar 

  59. Adam L, Vadlamudi R, Kondapaka SB, Chernoff J, Mendelsohn J, Kumar R. Heregulin regulates cytoskeletal reorganization and cell migration through the p21-activated kinase-1 via phosphatidylinositol-3 kinase. JBiol Chem 1998; 273: 28238–28246.

    Article  CAS  Google Scholar 

  60. Chausovsky A, Waterman H, Elbaum M, Yarden Y, Geiger B, Bershadsky AD. Molecular requirements for the effect of neuregulin on cell spreading, motility and colony organization. Oncogene 2000; 19: 878–888.

    Article  PubMed  CAS  Google Scholar 

  61. Tanno S, Tanno S, Mitsuuchi Y, Altomare DA, Xiao GH, Testa JR. AKT activation up-regulates insulin-like growth factor I receptor expression and promotes invasiveness of human pancreatic cancer. Cancer Res 2001; 61: 589–593.

    PubMed  CAS  Google Scholar 

  62. Yen L, You XL, Al Moustafa AE, Batist G, Hynes NE, Mader S, et al. Heregulin selectively upregulates vascular endothelial growth factor secretion in cancer cells and stimulates angiogenesis. Oncogene 2000; 19: 3460–2369.

    Article  PubMed  CAS  Google Scholar 

  63. Petit AM, Rak J, Hung MC, Rockwell P, Goldstein N, Fendly B, et al. Neutralizing antibodies against epidermal growth factor and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solids tumors. Am J Pathol 1997; 151: 1523–1530.

    PubMed  CAS  Google Scholar 

  64. Pegram MD, Slamon DJ. Combination therapy with trastuzumab (Herceptin) and cisplatin for chemoresistant metastatic breast cancer: evidence for receptor-enchanced chemosensitivity. Semin Oncol 1999; 26: 89–95.

    PubMed  CAS  Google Scholar 

  65. Lane HA, Beuvink I, Motoyama AB, Daly JM, Neve RM, Hynes NE. ErbB2 potentiates breast tumor proliferation through modulation of p27(Kip1)-Cdk2 complex formation: receptor overexpression does not determine growth dependency. Mol Cell Biol 2000; 20: 3210–3223.

    Article  PubMed  CAS  Google Scholar 

  66. Busse D, Doughty RS, Ramsey TT, Russell WE, Price JO, Flanagan WM, Reversible G(1) arrest induced by inhibition of the epidermal growth factor receptor tyrosine kinase requires up-regulation of p27(KIP1) independent of MAPK activity. J Biol Chem 2000; 275: 6987–6995.

    Article  PubMed  CAS  Google Scholar 

  67. Kumar R, Shepard HM, Mendelsohn J. Regulation of phosphorylation of the c-erbB-2/HER2 gene product by a monoclonal antibody and serum growth factor(s) in human mammary carcinoma cells. Mol Cell Biol 1991; 11: 979–986.

    PubMed  CAS  Google Scholar 

  68. Sarup JC, Johnson RM, King KL, Fendly BM, Lipari MT, Napier MA, et al. Characterization of an anti-p185HER2 monoclonal antibody that stimulates receptor function and inhibits tumor cell growth. Growth Reg 1991; 1: 72–82.

    CAS  Google Scholar 

  69. Klapper LN, Vaisman N, Hurwitz E, Pinkas-Kramarski R, Yarden Y, Sela M. A subclass of tumor-inhibitory monoclonal antibodies to ErbB-2/HER2 blocks crosstalk with growth factor receptors. Oncogene 1997; 14: 2099–2109.

    Article  PubMed  CAS  Google Scholar 

  70. Baulida J, Kraus MH, Alimandi M, Di Fiore PP, Carpenter G. All ErbB receptors other than the epidermal growth factor receptor are endocytosis impaired. J Biol Chem 1996; 271: 5251–5257.

    Article  PubMed  CAS  Google Scholar 

  71. Hudziak RM, Lewis GD, Winget M, Fendly BM, Shepard HM, Ullrich A. p185HER2 monoclonal antibody has antiproliferative effects in vitro and sensitizes human breast tumor cells to tumor necrosis factor. Mol Cell Biol 1989; 9: 1165–1172.

    PubMed  CAS  Google Scholar 

  72. De Santes K, Slamon D, Anderson SK, Shepard M, Fendly B, Maneval D, et al. Radiolabeled antibody targeting of the HER-2/neu oncoprotein. Cancer Res 1992; 52: 1916–1923.

    PubMed  Google Scholar 

  73. Maier LA, Xu FJ, Hester S, Boyer CM, McKenzie S, Bruskin AM, et al. Requirements for the internalization of a murine monoclonal antibody directed against the HER-2/neu gene product c-erbB-2. Cancer Res 1991; 51: 5361–5369.

    PubMed  CAS  Google Scholar 

  74. Waterman H, Yarden Y. Molecular mechanisms underlying endocytosis and sorting of ErbB receptor tyrosine kinases. FEBS Lett 2001; 490: 142–152.

    Article  PubMed  CAS  Google Scholar 

  75. Waterman H, Levkowitz G, Alroy I, Yarden Y. The RING finger of c-Cbl mediates desensitization of the epidermal growth factor receptor. J Biol Chem 1999; 274: 22151–22154.

    Google Scholar 

  76. Klapper LN, Waterman H, Sela M, Yarden Y. Tumor-inhibitory antibodies to HER-2/ErbB-2 may act by recruiting c-Cbl and enhancing ubiquitination of HER-2. Cancer Res 2001; 60: 3384–3388.

    Google Scholar 

  77. Aboud-Pirak E, Hurwitz E, Pirak ME, Bellot F, Schlessinger J, Sela M. Efficacy of antibodies to epidermal growth factor receptor against KB carcinoma in vitro and in nude mice. J Natl Cancer Inst 1988; 80: 1605–1611.

    Article  PubMed  CAS  Google Scholar 

  78. Hancock MC, Langton BC, Chan T, Toy P, Monahan JJ, Mischak RP, et al. 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 1991; 51: 4574–4580.

    Google Scholar 

  79. Arteaga CL, Winnier AR, Poirier MC, Lopez-Larraza DM, Shawver LK, Hurd SD, et al. p185c-erbB2 signal enhances cisplatin-induced cytotoxicity in human breast carcinoma cells: association between an oncogenic receptor tyrosine kinase and drug-induced DNA repair. Cancer Res 1994; 54: 3758–3765.

    PubMed  CAS  Google Scholar 

  80. Pegram MD, Lipton A, Hayes DF, Weber BL, Baselga JM, Tripathy D, et al. Phase II study of receptor-enhanced chemosensitivity using recombinant humanized anti-p185 HER2/neu monoclonal antibody plus cisplatin in patients with HER-2/neu-overexpressing metastatic breast cancer refractory to chemotherapy treatment. J Clin Oncol 1998; 16: 2659–2671.

    PubMed  CAS  Google Scholar 

  81. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regal 1984; 22: 27–55.

    Article  CAS  Google Scholar 

  82. Konecny G, Pegram M, Beryt M, Untch M, Slamon DJ. Therapeutic advantage of chemotherapy durgs in combination withe Herceptin against human breast cancer cells with HER-2/neu overexpression. Breast Cancer Res Treat 1999; 57: 114 (abstr 467).

    Google Scholar 

  83. Pegram M, Hsu S, Lewis G, Pietras R, Beryt M, Sliwkowski M, et al. Inhibitory effects of combinations of HER-2/neu antibody and chemotherapeutic agents used for treatment of human breast cancers. Oncogene 1999; 18: 2241–2251.

    Article  PubMed  CAS  Google Scholar 

  84. Baselga J, Tripathy D, Mendelsohn J, Baughman S, Benz CC, Dantis L, et al. Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol 1996; 14: 737–744.

    PubMed  CAS  Google Scholar 

  85. Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, et al. Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999; 17 (9): 2639–2648.

    PubMed  CAS  Google Scholar 

  86. Vogel CL, Cobleigh MA, Tripathy D, Gutheil JC, Harris LN, Fehrenbacher L, et al. Efficacy and safety of trastuzumab as a single agent in first-line treatment of HER2-overexpressing metastatic breast cancer. J Clin Oncol 2002; 20 (3): 719–726.

    Article  PubMed  CAS  Google Scholar 

  87. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A, et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl JMed 2001; 344: 783–792.

    Article  CAS  Google Scholar 

  88. Ito H, Miller SC, Billingham ME, Akimoto H, Torti SV, Wade R, et al. Doxorubicin selectively inhibits muscle gene expression in cardiac muscle cells in vivo and in vitro. Proc NaltAcad Sci USA 1990; 87: 4275–4279.

    Article  CAS  Google Scholar 

  89. Kunisada K, Tone E, Fujio Y, Matsui H, Yamauchi-Takihara K, Kishimoto T. Activation of gp130 transducer hypertrophic signals via STAT3 in cardiac myocytes. Circulation 1998; 98: 346–352.

    Article  PubMed  CAS  Google Scholar 

  90. Hunter JJ, Chien KR. Signaling pathways for cardiac hypertrophy and failure N Engl J Med 1999; 341: 1276–1283.

    Article  PubMed  CAS  Google Scholar 

  91. Chien KR. Myocyte survival pathways and cardiomyopathy:implications for trastuzumab cardiotoxicity. Semin Oncol 2000; 27: 9–14.

    PubMed  CAS  Google Scholar 

  92. Qiu Y, Ravi L, Kung HJ. Requirement of ErbB2 for signalling by interleukin-6 in prostate carcinoma cells. Nature 1998; 393: 83–85.

    Article  PubMed  CAS  Google Scholar 

  93. Zhao YY, Sawyer DR, Baliga RR, Opel DJ, Han X, Marchionni MA, et al. Neuregulins promote survival and growth of cardiac myocytes. Persistence of ErbB2 and ErbB4 expression in neonatal and adult ventricular myocytes. J Biol Chem 1998; 273: 10261–10269.

    Article  PubMed  CAS  Google Scholar 

  94. Pauletti G, Godolphin W, Press MF, Slamon DJ. Detection and quantitation of HER-2/neu gene amplification in human breast cancer archival material using fluorescence in situ hybridization. Oncogene 1996; 13: 63–72.

    PubMed  CAS  Google Scholar 

  95. Kallioniemi OP, Kallioniemi A, Kurisu W, Thor A, Chen LC, Smith HS, et al. ERBB2 amplification in breast cancer analyzed by fluorescence in situ hybridizaiton. Proc Natl Acad Sci USA 1992; 89: 5321–5325.

    Article  PubMed  CAS  Google Scholar 

  96. Mass RD, Sanders C, Charlene K, Johnson L, Everett T, Anderson S. The concordance between the clinical trials assay (CTA) and fluorescence in situ hybridization (FISH) in the Herceptin pivotal trials. Proc Am Soc Clin Oncol 2000; 19: 291 (abstr).

    Google Scholar 

  97. Mass RD, Press M, Anderson S, Murphy M, Slamon D. Improved survival benefit from Herceptin (Trastuzumab) in patients selected by fluorescence in site hybridization (FISH). Proc Am Soc Clin Oncol 2001; 20: 22a (abstra 85).

    Google Scholar 

  98. Vogel C, Cobleigh M, Tripathy D, Mass R, Murphy M, Stewart SJ. Superior outcomes with Herceptin (trastuzumab) (H) in fluorescence in situ hybridization (FISH)-selected patients. Proc Am Soc Clin Oncol 2001; 20: 22a (abstra 86).

    Google Scholar 

  99. Burstein HJ, Kuter I, Campos SM, Gelman RS, Tribou L, Parker LM, et al. Clinical activity of trastuzumab and vinorelbine in women with HER2-overexpressing metastatic breast cancer. J Clin Oncol 2001; 19 (10): 2722–2730.

    PubMed  CAS  Google Scholar 

  100. Slamon DJ, Patel R, Northfelt R, Pegram M, Rubin J, Sebastian G, et al. Phase II pilot study of herceptin combined with taxotere and carboplatin (TCH) in metastatic breast cancer (MBC) patients overexpressing the HER2-neu proto-oncogene: a pilot study of the UCLA network. Proc Am Soc Clin Oncol 2001; 20: 49a (abstr 193).

    Google Scholar 

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Authors
  1. Gottfried E. Konecny MD
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  2. Jane Arboleda PhD
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  3. Dennis J. Slamon MD, PhD
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  4. Mark Pegram MD
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Editors and Affiliations

  1. Henderson Research Centre, Department of Medicine, McMaster University, Hamilton, Ontario, Canada

    Janusz Rak MD, PhD

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Konecny, G.E., Arboleda, J., Slamon, D.J., Pegram, M. (2003). Inhibition of the HER-2/neu Oncogene. In: Rak, J. (eds) Oncogene-Directed Therapies. Cancer Drug Discovery and Development. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-313-2_16

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  • DOI: https://doi.org/10.1007/978-1-59259-313-2_16

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-4684-9738-0

  • Online ISBN: 978-1-59259-313-2

  • eBook Packages: Springer Book Archive

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