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Overexpression of ErbB2 in cancer and ErbB2-targeting strategies

Oncogene volume 19, pages 6115–6121 (2000)Cite this article

Abstract

This past decade has witnessed the remarkable advances in the understanding of the role of the erbB2 gene in cancers and the stunning progress in developing targeted therapies for erbB2-overexpressing cancers. Activation of the ErbB2 receptor signaling pathways can enhance various metastasis-associated properties that lead to an increase of cancer metastasis. Additionally, ErbB2 overexpression confers therapeutic resistance via receptor-mediated antiapoptotic signals. To limit these disastrous effects of the overexpressed ErbB2, various ErbB2-blocking strategies have been developed in the laboratories and several have been tested in clinical trials or approved as therapies for ErbB2 overexpressing cancers. In this article, we will discuss the detrimental effects of the erbB2 gene in cancers, with a focus on breast cancer. We will also outline ErbB2-targeting strategies as potential therapies for ErbB2-overexpressing cancers. Progress in understanding the molecular biology of ErbB2 and in molecular-based treatment of ErbB2-overexpressing tumors will bring great benefits to cancer patients.

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References

  • Akiyama T, Sudo C, Ogawara H, Toyoshima K and Yamamoto T. . 1986 Science 232: 1644–1646.

  • Amici A, Smorlesi A, Noce G, Santoni G, Cappelletti P, Capparuccia L, Coppari R, Lucciarini R, Petrelli C and Provinciali M. . 2000 Gene Ther. 7: 703–706.

  • Bargmann CI, Hung M-C and Weinberg RA. . 1986 Nature 319: 226–230.

  • Barnes MN, Deshane JS, Siegal GP, Alvarez RD and Curiel DT. . 1996 Clin. Cancer Res. 2: 1089–1095.

  • Baselga J, Norton L, Albanell J, Kim Y-M and Mendelsohn J. . 1998 Cancer Res. 58: 2825–2831.

  • Baselga J, Tripathy D, Mendelsohn J, Baughman S, Benz CC, Dantis L, Sklarin NT, Seidman AD, Hudis CA, Moore J, Rosen PP, Twaddell T, Henderson IC and Norton L. . 1996 J. Clin. Oncol. 14: 737–744.

  • Benz CC, Scott GK, Sarup JC, Johnson RM, Tripathy D, Coronado E, Shepard HM and Osborne CK. . 1992 Breast Cancer Res. Treat. 24: 85–95.

  • Berchuck A, Kamel A, Whitaker R, Kerns B, Olt G, Kinney R, Soper JT, Dodge R, Clarke-Pearson DL, Marks P, McKenzie P, Yin S and Bast JRC. . 1990 Cancer Res. 50: 4087–4091.

  • Borg A, Baldetorp B, Ferno M, Killander D, Olsson H, Ryden S and Sigurdsson H. . 1994 Cancer Lett. 81: 137–144.

  • Burke HB, Hoang A, Iglehart JD and Marks JR. . 1998 Cancer 82: 874–877.

  • Carraway III KL, Rossi EA, Komatsu M, Price-Schiavi SA, Huang D, Guy PM, Carvajal ME, Fregien N, Carraway CAC and Carraway KL. . 1999 J. Biol. Chem. 274: 5263–5266.

  • Carraway KL, Sliwkowski MX, Akita R, Platko JV, Guy PM, Nuijens A, Diamonti J, Vandelen RL, Cantley LC and Cerione RA. . 1994 J. Biol. Chem. 269: 14303–14306.

  • Colomer R, Montero S, Lluch A, Ojeda B, Barnadas A, Casado A, Massuti B, Cortes-Funes H and Lloveras B. . 2000 Clin. Cancer Res. 6: 2356–2362.

  • Coussens L, Yang-Feng TL, Liao Y-C, Chen E, Gray A, McGrath J, Seeburg PH, Libermann TA, Schlessinger J, Francke U, Levinson A and Ullrich A. . 1985 Science 230: 1132–1139.

  • Craft N, Shostak Y, Carey M and Sawyers CL. . 1999 Nat. Med. 5: 280–285.

  • Deng J, Xia W and Hung M-C. . 1998 Oncogene 17: 2167–2175.

  • Deshane J, Grim J, Loechel S, Siegal GP, Alvarez RD and Curiel DT. . 1996 Cancer Gene Ther. 3: 89–98.

  • Drebin JA, Link VC and Greene MI. . 1998a Oncogene 2: 273–277.

  • Drebin JA, Link VC and Greene MI. . 1998b Oncogene 2: 387–394.

  • Drebin JA, Link VC, Stern DF, Weinberg RA and Greene MI. . 1985 Cell 41: 695–706.

  • Drebin JA, Link VC, Weinberg RA and Greene MI. . 1986 Natl. Acad. Sci. USA 83: 9129–9133.

  • Fehm T, Maimonis P, Katalinic A and Jager WH. . 1998 Oncology 55: 33–38.

  • Fehm T, Maimonis P, Weitz S, Teramoto Y, Katalinic A and Jager W. . 1997 Breast Cancer Res. Treat. 43: 87–95.

  • Frisch SM. . 1991 Proc. Natl. Acad. Sci. USA 88: 9077–9081.

  • Frisch SM and Dolter KE. . 1995 Cancer Res. 55: 5551–5555.

  • Fry DW, Bridges AJ, Denny WA, Doherty A, Greis KD, Hicks JL, Hook KE, Keller PR, Leopold WR, Loo JA, McNamara DJ, Nelson JM, Sherwood V, Smaill JB, Trumpp-Kallmeyer S and Dobrusin EM. . 1998 Proc. Natl. Acad. Sci. USA 95: 12022–12027.

  • Giannois J and Ioannidou-Mouzaka L. . 1997 Eur. J. Gynaecol. Oncol. 18: 387–393.

  • Graus-Porta D, Beerli RR, Daly JM and Hynes NE. . 1997 EMBO J. 16: 1647–1655.

  • Grunt T, Dittrich E, Ofterdinger M, Schneider SM, Dittrich C and Huber H. . 1998 Br. J. Cancer 78: 79–87.

  • Gusterson BA, Gelber RD, Goldhirsch A, Price KN, Save-Soderborgh J, Anbazhagan R, Styles J, Rudenstam C-M, Golouh R, Reed R, Martinez-Tello F, Tiltman A, Torhorst J, Grigolato P, Bettelheim R, Neville AM, Burki K, Castiglione M, Collins J, Lindtner J, Senn H-J and Ludwig IBCSG. . 1992 J. Clin. Oncol. 10: 1049–1056.

  • Guy CT, Webster MA, Schaller M, Parsons TJ, Cardiff RD and Muller WJ. . 1992 Proc. Natl. Acad. Sci. USA 89: 10578–10582.

  • Harris JD, Gutierrez AA, Hurst CC, Sikora K and Lemoine NR. . 1994 Gene Therapy 1: 170–175.

  • Haynes NM, Smyth MJ, Kershaw MH, Trapani JA and Darcy PK. . 1999 Cancer Immunol. Immunother. 47: 278–286.

  • Hong R-L, Spohn WH and Hung M-C. . 1999 Clin. Cancer Res. 5: 1884–1891.

  • Hudziak RM, Lewis GD, Shalaby MR, Eessalu TE, Aggarwal BB, Ullrich A and Shepard HM. . 1988 Proc. Natl. Acad. Sci. USA 85: 5102–5106.

  • Hung M-C, Wang S-C and Hortobagyi G. . 1999 Nonviral Vectors for Gene Therapy. Vol. 16. Huang L, Hung M-C and Wagner E (eds). Academic Press: San Diego pp 358–372.

  • Huston JS, McCartney J, Tai MS, Mottola-Hartshorn C, Jin D, Warren F, Keck P and Oppermann H. . 1993 Int. Rev. Immunol. 10: 195–217.

  • Jarvinen TA, Holli K, Kuukasjarvi T and Isola JJ. . 1998 Br. J. Cancer 77: 2267–2273.

  • King M-C. . 1998 Her-2.Bazell R. (ed). Random House: New York pp xi–xiii.

  • Leitzel K, Teramoto Y, Konrad K, Chinchilli VM, Volas G, Grossberg H, Harvey H, Demers L and Lipton A. . 1995 J. Clin. Oncol. 13: 1129–1135.

  • Lichtenstein A, Berenson J, Gera JF, Waldburger K, Martinez-Maza O and Berek J. . 1990 Cancer Res. 50: 7364–7370.

  • Mehta RR, McDermott JH, Hieken TJ, Marler KC, Patel MK and Wild LD. . 1998 J. Clin. Oncol. 16: 2409–2416.

  • Muss HB, Thor AD, Berry DA, Kute T, Liu ET, Koerner F, Cirrincione CT, Budman DR, Wood WC, Barcos M and Henderson IC. . 1994 N. Engl. J. Med. 330: 1260–1266.

  • Mymryk JS. . 1996 Oncogene 13: 1581–1589.

  • Nelson NJ. . 2000 J. Natl. Cancer Inst. 92: 366–367.

  • Noonberg SB and Benz CC. . 2000 Drugs 59: 753–767.

  • Pandha HS, Martin L-A, Rigg A, Hurst HC, Stamp GWH, Sikara K and Lemoine NR. . 1999 J. Clin. Oncol. 17: 2180–2189.

  • Park BW, Berezov A, Wu CW, Zhang X, Dua R, Zhang HT, Wang Q, Kao G, O'Rourke DM, Green MI and Murali R. . 2000 Nat. Biotech. 18: 194–198.

  • Pegram MD, Lipton A, Hayes DF, Weber BL, Baselga JM, Tripathy D, Baly D, Baughman SA, Twaddell T, Glaspy JA and Slamon DJ. . 1998 J. Clin. Oncol. 16: 2659–2671.

  • Petit AM, Rak J, Hung M-C, Rockwell P, Goldstein N, Fendly B and Kerbel RS. . 1997 Am. J. Pathol. 151: 1523–1530.

  • Pietras RJ, Arboleda J, Reese DM, Wongvipat N, Pegram MD, Ramos L, Gorman CM, Parker MG, Sliwkowski MX and Slamon DJ. . 1995 Oncogene 10: 2435–2446.

  • Pietras RJ, Pegram MD, Finn RS, Maneval DA and Slamon DJ. . 1998 Oncogene 17: 2235–2249.

  • Pirollo KF, Hao Z, Rait A, Ho CW and Chang EH. . 1997 Biochem. Biophys. Res. Commun. 230: 196–201.

  • Plowman GD, Grenn JM, Culouscou J-M, Carlton GW, Rothwell VM and Buckley S. . 1993 Nature 366: 473–475.

  • Rao GN, Ney E and Herbert RA. . 1999 Breast Cancer Res. Treat. 56: 241–254.

  • Russell KS and Hung MC. . 1992 Cancer Res. 52: 6624–6629.

  • Russell KS, Lee EK, Kiyokawa N, Hideyuki S and Hung MC. . 1996 Oncol. Reports 3: 433–437.

  • Samanta A, LeVea CM, Dougall WC, Qian X and Greene MI. . 1994 Proc. Natl. Acad. Sci. USA 91: 1711–1715.

  • Shao R, Hu MC-T, Zhou BP, Lin S-Y, Chiao P, von Lindern RH, Sporn B and Hung M-C. . 1999 J. Biol. Chem. 274: 21495–21498.

  • Shao R, Karunagaran D, Zhou BP, Li K, Lo S-S, Deng J, Chiao P and Hung M-C. . 1997 J. Biol. Chem. 272: 32739–32742.

  • Shepard HM, Lewis GD, Sarup JC, Fendly BM, Maneval D, Mordenti J, Figari I, Kotts CE, Palladino Jr MA, Ullrich A and Slamon D. . 1991 J. Clin. Immunol. 11: 117–127.

  • Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A and McGuire WL. . 1987 Science 235: 177–182.

  • Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A and McGuire WL. . 1989 Science (Washington, DC) 244: 707–712.

  • Stern DF, Heffernan PA and Weinberg RA. . 1986 Mol. Cell. Biol. 6: 1729–1740.

  • Suda Y, Aizawa S, Furuta Y, Yagi T, Ikawa Y, Saitoh K, Yamada Y, Toyoshima K and Yamamoto T. . 1990 EMBO J. 9: 181–190.

  • Tan M, Yao J and Yu D. . 1997 Cancer Res. 57: 1199–1205.

  • Tetu B and Brisson J. . 1994 Cancer 73: 2359–2365.

  • Ueno NT, Yu D and Hung MC. . 1997 Oncogene 15: 953–960.

  • van Agthoven T, van Agthoven TL, Dekker A, Foekens JA and Dorssers LC. . 1994 Mol. Endocrinol. 8: 1474–1483.

  • Wright M, Grim J, Deshane J, Kim M, Strong TV, Siegal GP and Curiel DT. . 1997 Gene Ther. 4: 317–322.

  • Xing X, Wang S-C, Xia W, Zou Y, Shao R, Kwong KY, Yu Z, Zhang S, Miller S, Huang L and Hung M-C. . 2000 Nat. Med. 6: 189–195.

  • Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, Saito T and Toyoshima K. . 1986 Nature 319: 230–234.

  • Yamauchi H, O'Neill A, Gelman R, Carney W, Tenney DY, Hosch S and Hayes DF. . 1997 J. Clin. Oncol. 15: 2518–2525.

  • Yu D and Hung M-C. . 1995 Molecular Basis of Oncology. Vol. 5. Freireich E and Stass SA (eds). Blackwell Scientific Publications Inc.: Cambridge pp 131–162.

  • Yu D and Hung M-C. . 2000 BioEssays 22: 673–680.

  • Yu D and Hung MC. . 1991 Oncogene 6: 1991–1996.

  • Yu D, Jing T, Liu B, Yao J, Tan M, McDonnell TJ and Hung M-C. . 1998a Mol. Cell 2: 581–591.

  • Yu D, Liu B, Sun D, Jing T, Price JE, Singletary SE, Hortobagyi GN and Hung M-C. . 1998b Oncogene 16: 2087–2094.

  • Yu D, Liu B, Tan M, Li J, Wang S-S and Hung M-C. . 1996 Oncogene 13: 1359–1365.

  • Yu D, Matin A, Xia W, Sorgi F, Huang L and Hung M-C. . 1995 Oncogene 11: 1383–1388.

  • Yu D, Scorsone K and Hung M-C. . 1991 Mol. Cell. Biol. 11: 1745–1750.

  • Yu D, Suen T-C, Yan D-H, Chang LS and Hung M-C. . 1990 Proc. Natl. Acad. Sci. USA 87: 4499–4503.

  • Yu D, Wang S-S, Dulski KM, Tsai C-M, Nicolson GL and Hung M-C. . 1994 Cancer Res. 54: 3260–3266.

  • Yu DH, Hamada JI, Zhang H, Nicolson GL and Hung M-C. . 1992 Oncogene 7: 2263–2270.

  • Zhang L, Chang CJ, Bacus SS and Hung M-C. . 1995 Cancer Res. 55: 3890–3896.

  • Zhang Y, Xia W, Shao R, Sorgi F, Hortobagyi GN, Huang L and Hung M-C. . 1997 Oncogene 14: 561–568.

  • Zhou BP, Hu MC-T, Miller SA, Yu Z, Xia W, Lin S-Y and Hung MC. . 2000 J. Biol. Chem. 275: 8027–8031.

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Acknowledgements

The authors thank Dr Jun Yao for assistance in generating the computer artwork of Figure 1 and Mr Christopher Neal for reading of the manuscript. This work was supported by NIH grants 2RO1CA60488 (D Yu), RO1CA58880 (M-C Hung), RO1CA60856 (M-C Hung), by USAMRMC grants DAMD17-98-8338 (D Yu), DAMD17-99-9271 (D Yu), DAMD-17-00-1-0312-1 (M-C Hung), and by M.D. Anderson Breast Cancer Research Program Fund.

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  1. Department of Surgical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, Texas, U.S.A.

    Dihua Yu & Mien-Chie Hung

  2. Department of Molecular and Cellular Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, Texas, U.S.A.

    Dihua Yu & Mien-Chie Hung

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Yu, D., Hung, MC. Overexpression of ErbB2 in cancer and ErbB2-targeting strategies. Oncogene 19, 6115–6121 (2000). https://doi.org/10.1038/sj.onc.1203972

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