Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review
  • Published:

Gene therapy for carcinoma of the breast

Cancer Gene Therapy volume 13, pages 633–647 (2006)Cite this article

Abstract

In view of the limited success of available treatment modalities for breast cancer, alternative and complementary strategies need to be developed. The delineation of the molecular basis of breast cancer provides the possibility of specific intervention by gene therapy through the introduction of genetic material for therapeutic purposes. In this regard, several gene therapy approaches for carcinoma of the breast have been developed. These approaches can be divided into six broad categories: (1) mutation compensation, (2) molecular chemotherapy, (3) proapoptotic gene therapy, (4) antiangiogenic gene therapy, (5) genetic immunopotentiation, and (6) genetic modulation of resistance/sensitivity. Clinical trials for breast cancer have been initiated to evaluate safety, toxicity, and efficacy. Combined modality therapy with gene therapy and chemotherapy or radiation therapy has shown promising results. It is expected that as new therapeutic targets and approaches are identified and advances in vector design are realized, gene therapy will play an increasing role in clinical breast cancer treatment.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Lacey Jr JV, Devesa SS, Brinton LA . Recent trends in breast cancer incidence and mortality. Environ Mol Mutagen 2002; 39: 82–88.

    Article  CAS  PubMed  Google Scholar 

  2. Osborne RJ, Hamshere MG . A genome-wide map showing common regions of loss of heterozygosity/allelic imbalance in breast cancer. Cancer Res 2000; 60: 3706–3712.

    CAS  PubMed  Google Scholar 

  3. Miller BJ, Wang D, Krahe R, Wright FA . Pooled analysis of loss of heterozygosity in breast cancer: a genome scan provides comparative evidence for multiple tumor suppressors and identifies novel candidate regions. Am J Hum Genet 2003; 73: 748–767.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Dickson RBLM . Growth regulation of normal and malignant breast epithelium. In: Bland KI, Copeland III EM (eds). The Breast: Comprehensive Management of Benign and Malign Diseases, 2nd edn. WB Saunders: Philadelphia, 1998, pp 518–563.

    Google Scholar 

  5. Knudson Jr AG . Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 1971; 68: 820–823.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Johannsdottir HK, Johannesdottir G, Agnarsson BA, Eerola H, Arason A, Johannsson OT et al. Deletions on chromosome 4 in sporadic and BRCA mutated tumors and association with pathological variables. Anticancer Res 2004; 24: 2681–2687.

    CAS  PubMed  Google Scholar 

  7. Trent JMYJ, Thompson FH, Leibowitz A, Villar H, Dalton WS . Chromosomal alterations in human breast cancer. In: M Sluyser (ed). Growth Factors and Oncogenes in Breast Cancer. Ellis Horwood: Chichester, UK, 1987, pp 142–151.

    Google Scholar 

  8. Cleton-Jansen AM, Buerger H, Haar N, Philippo K, van de Vijver MJ, Boecker W et al. Different mechanisms of chromosome 16 loss of heterozygosity in well- versus poorly differentiated ductal breast cancer. Genes Chromosomes Cancer 2004; 41: 109–116.

    Article  CAS  PubMed  Google Scholar 

  9. Osborne C, Wilson P, Tripathy D . Oncogenes and tumor suppressor genes in breast cancer: potential diagnostic and therapeutic applications. Oncologist 2004; 9: 361–377.

    Article  CAS  PubMed  Google Scholar 

  10. Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 1994; 266: 66–71.

    Article  CAS  PubMed  Google Scholar 

  11. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science 1990; 250: 1684–1689.

    Article  CAS  PubMed  Google Scholar 

  12. Phelan CM, Lancaster JM, Tonin P, Gumbs C, Cochran C, Carter R et al. Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families. Nat Genet 1996; 13: 120–122.

    Article  CAS  PubMed  Google Scholar 

  13. de Jong MM, Nolte IM, te Meerman GJ, van der Graaf WT, Oosterwijk JC, Kleibeuker JH et al. Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility. J Med Genet 2002; 39: 225–242.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lancaster JM, Wooster R, Mangion J, Phelan CM, Cochran C, Gumbs C et al. BRCA2 mutations in primary breast and ovarian cancers. Nat Genet 1996; 13: 238–240.

    Article  CAS  PubMed  Google Scholar 

  15. Lacroix M, Leclercq G . The ‘portrait’ of hereditary breast cancer. Breast Cancer Res Treat 2005; 89: 297–304.

    Article  CAS  PubMed  Google Scholar 

  16. Deng CX, Brodie SG . Roles of BRCA1 and its interacting proteins. BioEssays 2000; 22: 728–737.

    Article  CAS  PubMed  Google Scholar 

  17. Lee WH, Bookstein R, Hong F, Young LJ, Shew JY, Lee EY . Human retinoblastoma susceptibility gene: cloning, identification, and sequence. Science 1987; 235: 1394–1399.

    Article  CAS  PubMed  Google Scholar 

  18. Andersen TI, Gaustad A, Ottestad L, Farrants GW, Nesland JM, Tveit KM et al. Genetic alterations of the tumour suppressor gene regions 3p, 11p, 13q, 17p, and 17q in human breast carcinomas. Genes Chromosomes Cancer 1992; 4: 113–121.

    Article  CAS  PubMed  Google Scholar 

  19. Takahashi T, Nau MM, Chiba I, Birrer MJ, Rosenberg RK, Vinocour M et al. p53: a frequent target for genetic abnormalities in lung cancer. Science 1989; 246: 491–494.

    Article  CAS  PubMed  Google Scholar 

  20. Malkin D . Germline p53 mutations and heritable cancer. Annu Rev Genet 1994; 28: 443–465.

    Article  CAS  PubMed  Google Scholar 

  21. Hollstein M, Sidransky D, Vogelstein B, Harris CC . p53 mutations in human cancers. Science 1991; 253: 49–53.

    Article  CAS  PubMed  Google Scholar 

  22. Bland KI . The 1999 James Ewing Lecture: in pursuit of molecules of oncogenesis and neoplastic therapy. Ann Surg Oncol 1999; 6: 528–541.

    Article  CAS  PubMed  Google Scholar 

  23. King CR, Kraus MH, Aaronson SA . Amplification of a novel v-erbB-related gene in a human mammary carcinoma. Science 1985; 229: 974–976.

    Article  CAS  PubMed  Google Scholar 

  24. Funkhouser WK, Kaiser-Rogers K . Review: significance of, and optimal screening for, HER-2 gene amplification and protein overexpression in breast carcinoma. Ann Clin Lab Sci 2001; 31: 349–358.

    CAS  PubMed  Google Scholar 

  25. Nass SJ, Dickson RB . Defining a role for c-Myc in breast tumorigenesis. Breast Cancer Res Treat 1997; 44: 1–22.

    Article  CAS  PubMed  Google Scholar 

  26. Varley JM SJ, Brammer WJ . Alerations to either c-erbB2(neu) or c-myc proto-oncogenes in breast carcinoma correlate with poor short-term prognosis. Oncogene 1987; 1: 423–430.

    PubMed  Google Scholar 

  27. Boveri T . The Origin of Malignant Tumors. Williams and Wilkins: Baltimore, MD, 1929.

    Google Scholar 

  28. Jiang Z, Zacksenhaus E . Activation of retinoblastoma protein in mammary gland leads to ductal growth suppression, precocious differentiation, and adenocarcinoma. J Cell Biol 2002; 156: 185–198.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Wang NP, To H, Lee WH, Lee EY . Tumor suppressor activity of RB and p53 genes in human breast carcinoma cells. Oncogene 1993; 8: 279–288.

    CAS  PubMed  Google Scholar 

  30. Bai J, Zhu X, Zheng X, Wu Y . Retroviral vector containing human p16 gene and its inhibitory effect on Bcap-37 breast cancer cells. Chin Med J (England) 2001; 114: 497–501.

    CAS  Google Scholar 

  31. Campbell I, Magliocco A, Moyana T, Zheng C, Xiang J . Adenovirus-mediated p16INK4 gene transfer significantly suppresses human breast cancer growth. Cancer Gene Ther 2000; 7: 1270–1278.

    Article  CAS  PubMed  Google Scholar 

  32. Craig C, Wersto R, Kim M, Ohri E, Li Z, Katayose D et al. A recombinant adenovirus expressing p27Kip1 induces cell cycle arrest and loss of cyclin-Cdk activity in human breast cancer cells. Oncogene 1997; 14: 2283–2289.

    Article  CAS  PubMed  Google Scholar 

  33. Shibata MA, Yoshidome K, Shibata E, Jorcyk CL, Green JE . Suppression of mammary carcinoma growth in vitro and in vivo by inducible expression of the Cdk inhibitor p21. Cancer Gene Ther 2001; 8: 23–35.

    Article  CAS  PubMed  Google Scholar 

  34. McKenzie T, Liu Y, Fanale M, Swisher SG, Chada S, Hunt KK . Combination therapy of Ad-mda7 and trastuzumab increases cell death in Her-2/neu-overexpressing breast cancer cells. Surgery 2004; 136: 437–442.

    Article  PubMed  Google Scholar 

  35. Sauane M, Gopalkrishnan RV, Choo HT, Gupta P, Lebedeva IV, Yacoub A et al. Mechanistic aspects of mda-7/IL-24 cancer cell selectivity analysed via a bacterial fusion protein. Oncogene 2004; 23: 7679–7690.

    Article  CAS  PubMed  Google Scholar 

  36. Holt JT, Thompson ME, Szabo C, Robinson-Benion C, Arteaga CL, King MC et al. Growth retardation and tumour inhibition by BRCA1. Nat Genet 1996; 12: 298–302.

    Article  CAS  PubMed  Google Scholar 

  37. Holt JT . Breast cancer genes: therapeutic strategies. Ann NY Acad Sci 1997; 833: 34–41.

    Article  CAS  PubMed  Google Scholar 

  38. Shi HY, Liang R, Templeton NS, Zhang M . Inhibition of breast tumor progression by systemic delivery of the maspin gene in a syngeneic tumor model. Mol Ther 2002; 5: 755–761.

    Article  CAS  PubMed  Google Scholar 

  39. Sarti M, Sevignani C, Calin GA, Aqeilan R, Shimizu M, Pentimalli F et al. Adenoviral transduction of TESTIN gene into breast and uterine cancer cell lines promotes apoptosis and tumor reduction in vivo. Clin Cancer Res 2005; 11: 806–813.

    CAS  PubMed  Google Scholar 

  40. Chen QR, Mixson AJ . Systemic gene therapy with p53 inhibits breast cancer: recent advances and therapeutic implications. Front Biosci 1998; 3: D997–D1004.

    Article  CAS  PubMed  Google Scholar 

  41. Xu M, Kumar D, Srinivas S, Detolla LJ, Yu SF, Stass SA et al. Parenteral gene therapy with p53 inhibits human breast tumors in vivo through a bystander mechanism without evidence of toxicity. Hum Gene Ther 1997; 8: 177–185.

    Article  CAS  PubMed  Google Scholar 

  42. Reed JC, Miyashita T, Krajewski S, Takayama S, Aime-Sempe C, Kitada S et al. Bcl-2 family proteins and the regulation of programmed cell death in leukemia and lymphoma. Cancer Treat Res 1996; 84: 31–72.

    Article  CAS  PubMed  Google Scholar 

  43. Owen-Schaub LB, Zhang W, Cusack JC, Angelo LS, Santee SM, Fujiwara T et al. Wild-type human p53 and a temperature-sensitive mutant induce Fas/APO-1 expression. Mol Cell Biol 1995; 15: 3032–3040.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Molinier-Frenkel V, Le Boulaire C, Le Gal FA, Gahery-Segard H, Tursz T, Guillet JG et al. Longitudinal follow-up of cellular and humoral immunity induced by recombinant adenovirus-mediated gene therapy in cancer patients. Hum Gene Ther 2000; 11: 1911–1920.

    Article  CAS  PubMed  Google Scholar 

  45. Yen N, Ioannides CG, Xu K, Swisher SG, Lawrence DD, Kemp BL et al. Cellular and humoral immune responses to adenovirus and p53 protein antigens in patients following intratumoral injection of an adenovirus vector expressing wild-type P53 (Ad-p53). Cancer Gene Ther 2000; 7: 530–536.

    Article  CAS  PubMed  Google Scholar 

  46. McCormick F . Cancer gene therapy: fringe or cutting edge? Nat Rev Cancer 2001; 1: 130–141.

    Article  CAS  PubMed  Google Scholar 

  47. Zhang WW, Fang X, Mazur W, French BA, Georges RN, Roth JA . High-efficiency gene transfer and high-level expression of wild-type p53 in human lung cancer cells mediated by recombinant adenovirus. Cancer Gene Ther 1994; 1: 5–13.

    PubMed  Google Scholar 

  48. Nielsen LL, Dell J, Maxwell E, Armstrong L, Maneval D, Catino JJ . Efficacy of p53 adenovirus-mediated gene therapy against human breast cancer xenografts. Cancer Gene Ther 1997; 4: 129–138.

    CAS  PubMed  Google Scholar 

  49. National Institute of Health RDAC. Gene Therapy Protocols by Disease. NIH: Washington, DC, 2002.

  50. Dias N, Stein CA . Antisense oligonucleotides: basic concepts and mechanisms. Mol Cancer Ther 2002; 1: 347–355.

    Article  CAS  PubMed  Google Scholar 

  51. McManaway ME, Neckers LM, Loke SL, al-Nasser AA, Redner RL, Shiramizu BT et al. Tumour-specific inhibition of lymphoma growth by an antisense oligodeoxynucleotide. Lancet 1990; 335: 808–811.

    Article  CAS  PubMed  Google Scholar 

  52. Arteaga CL, Holt JT . Tissue-targeted antisense c-fos retroviral vector inhibits established breast cancer xenografts in nude mice. Cancer Res 1996; 56: 1098–1103.

    CAS  PubMed  Google Scholar 

  53. Townsend PA, Villanova I, Uhlmann E, Peyman A, Knolle J, Baron R et al. An antisense oligonucleotide targeting the alphaV integrin gene inhibits adhesion and induces apoptosis in breast cancer cells. Eur J Cancer 2000; 36: 397–409.

    Article  CAS  PubMed  Google Scholar 

  54. Gardner-Thorpe J, Ito H, Ashley SW, Whang EE . Ribosomal protein P2: a potential molecular target for antisense therapy of human malignancies. Anticancer Res 2003; 23: 4549–4560.

    CAS  PubMed  Google Scholar 

  55. Brysch W, Magal E, Louis JC, Kunst M, Klinger I, Schlingensiepen R et al. Inhibition of p185c-erbB-2 proto-oncogene expression by antisense oligodeoxynucleotides down-regulates p185-associated tyrosine-kinase activity and strongly inhibits mammary tumor-cell proliferation. Cancer Gene Ther 1994; 1: 99–105.

    CAS  PubMed  Google Scholar 

  56. Sekhon J, Pereira P, Sabbaghian N, Schievella AR, Rozen R . Antisense inhibition of methylenetetrahydrofolate reductase reduces survival of methionine-dependent tumour lines. Br J Cancer 2002; 87: 225–230.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Fan Y, Borowsky AD, Weiss RH . An antisense oligodeoxynucleotide to p21(Waf1/Cip1) causes apoptosis in human breast cancer cells. Mol Cancer Ther 2003; 2: 773–782.

    CAS  PubMed  Google Scholar 

  58. Roychowdhury D, Lahn M . Antisense therapy directed to protein kinase C-alpha (Affinitak, LY900003/ISIS 3521): potential role in breast cancer. Semin Oncol 2003; 30: 30–33.

    Article  CAS  PubMed  Google Scholar 

  59. Lahn M, Kohler G, Sundell K, Su C, Li S, Paterson BM et al. Protein kinase C alpha expression in breast and ovarian cancer. Oncology 2004; 67: 1–10.

    Article  CAS  PubMed  Google Scholar 

  60. Nahta R, Esteva FJ . Bcl-2 antisense oligonucleotides: a potential novel strategy for the treatment of breast cancer. Semin Oncol 2003; 30: 143–149.

    Article  CAS  PubMed  Google Scholar 

  61. Natarajan S, Chen Z, Wancewicz EV, Monia BP, Corey DR . Telomerase reverse transcriptase (hTERT) mRNA and telomerase RNA (hTR) as targets for downregulation of telomerase activity. Oligonucleotides 2004; 14: 263–273.

    Article  CAS  PubMed  Google Scholar 

  62. Lee WJ, Robinson JA, Holman NA, McCall MN, Roberts-Thomson SJ, Monteith GR . Antisense mediated inhibition of the plasma membrane calcium-ATPase suppresses proliferation of MCF-7 cells. J Biol Chem 2005; 280: 27076–27084.

    Article  CAS  PubMed  Google Scholar 

  63. Salatino M, Schillaci R, Proietti CJ, Carnevale R, Frahm I, Molinolo AA et al. Inhibition of in vivo breast cancer growth by antisense oligodeoxynucleotides to type I insulin-like growth factor receptor mRNA involves inactivation of ErbBs, PI-3K/Akt and p42/p44 MAPK signaling pathways but not modulation of progesterone receptor activity. Oncogene 2004; 23: 5161–5174.

    Article  CAS  PubMed  Google Scholar 

  64. Scherr M, Morgan MA, Eder M . Gene silencing mediated by small interfering RNAs in mammalian cells. Curr Med Chem 2003; 10: 245–256.

    Article  CAS  PubMed  Google Scholar 

  65. Shuey DJ, McCallus DE, Giordano T . RNAi: gene-silencing in therapeutic intervention. Drug Discov Today 2002; 7: 1040–1046.

    Article  CAS  PubMed  Google Scholar 

  66. Wang YH, Liu S, Zhang G, Zhou CQ, Zhu HX, Zhou XB et al. Knockdown of c-Myc expression by RNAi inhibits MCF-7 breast tumor cells growth in vitro and in vivo. Breast Cancer Res 2005; 7: R220–R228.

    Article  CAS  PubMed  Google Scholar 

  67. Rossi JJ . Ribozymes. Curr Opin Biotechnol 1992; 3: 3–7.

    Article  CAS  PubMed  Google Scholar 

  68. Rossi JJ, Elkins D, Zaia JA, Sullivan S . Ribozymes as anti-HIV-1 therapeutic agents: principles, applications, and problems. AIDS Res Hum Retroviruses 1992; 8: 183–189.

    Article  CAS  PubMed  Google Scholar 

  69. Citti L, Rainaldi G . Synthetic hammerhead ribozymes as therapeutic tools to control disease genes. Curr Gene Ther 2005; 5: 11–24.

    Article  CAS  PubMed  Google Scholar 

  70. Suzuki T, Anderegg B, Ohkawa T, Irie A, Engebraaten O, Halks-Miller M et al. Adenovirus-mediated ribozyme targeting of HER-2/neu inhibits in vivo growth of breast cancer cells. Gene Therapy 2000; 7: 241–248.

    Article  CAS  PubMed  Google Scholar 

  71. Choi KS, Lee TH, Jung MH . Ribozyme-mediated cleavage of the human survivin mRNA and inhibition of antiapoptotic function of survivin in MCF-7 cells. Cancer Gene Ther 2003; 10: 87–95.

    Article  CAS  PubMed  Google Scholar 

  72. Iyo M, Kawasaki H, Taira K . Construction of an allosteric trans-maxizyme targeting for two distinct oncogenes. Nucleic Acids Res Suppl 2002; 2: 115–116.

    Article  CAS  Google Scholar 

  73. Wright M, Grim J, Deshane J, Kim M, Strong TV, Siegal GP et al. An intracellular anti-erbB-2 single-chain antibody is specifically cytotoxic to human breast carcinoma cells overexpressing erbB-2. Gene Therapy 1997; 4: 317–322.

    Article  CAS  PubMed  Google Scholar 

  74. Grim JE, Siegal GP, Alvarez RD, Curiel DT . Intracellular expression of the anti-erbB-2 sFv N29 fails to accomplish efficient target modulation. Biochem Biophys Res Commun 1998; 250: 699–703.

    Article  CAS  PubMed  Google Scholar 

  75. Yu D, Matin A, Hinds PW, Hung MC . Transcriptional regulation of neu by RB and E1A in rat-1 cells. Cell Growth Differ 1994; 5: 431–438.

    CAS  PubMed  Google Scholar 

  76. Nevins JR . Adenovirus E1A-dependent trans-activation of transcription. Semin Cancer Biol 1990; 1: 59–68.

    CAS  PubMed  Google Scholar 

  77. Chang JY, Xia W, Shao R, Sorgi F, Hortobagyi GN, Huang L et al. The tumor suppression activity of E1A in HER-2/neu-overexpressing breast cancer. Oncogene 1997; 14: 561–568.

    Article  CAS  PubMed  Google Scholar 

  78. Ueno NT, Yu D, Hung MC . E1A: tumor suppressor or oncogene? Preclinical and clinical investigations of E1A gene therapy. Breast Cancer 2001; 8: 285–293.

    Article  CAS  PubMed  Google Scholar 

  79. Niculescu-Duvaz I, Springer CJ . Introduction to the background, principles, and state of the art in suicide gene therapy. Mol Biotechnol 2005; 30: 71–88.

    Article  CAS  PubMed  Google Scholar 

  80. Gadal F, Bastias J, Wei MX, Crepin M . ‘Suicide’ gene therapy of breast cancer cells is only cytostatic in vitro but anti-tumoral in vivo on breast MCF7-ras tumor. In Vivo 2004; 18: 813–818.

    CAS  PubMed  Google Scholar 

  81. Grignet-Debrus C, Cool V, Baudson N, Velu T, Calberg-Bacq CM . The role of cellular- and prodrug-associated factors in the bystander effect induced by the Varicella zoster and Herpes simplex viral thymidine kinases in suicide gene therapy. Cancer Gene Ther 2000; 7: 1456–1468.

    Article  CAS  PubMed  Google Scholar 

  82. Friedlos F, Davies L, Scanlon I, Ogilvie LM, Martin J, Stribbling SM et al. Three new prodrugs for suicide gene therapy using carboxypeptidase G2 elicit bystander efficacy in two xenograft models. Cancer Res 2002; 62: 1724–1729.

    CAS  PubMed  Google Scholar 

  83. Stribbling SM, Friedlos F, Martin J, Davies L, Spooner RA, Marais R et al. Regressions of established breast carcinoma xenografts by carboxypeptidase G2 suicide gene therapy and the prodrug CMDA are due to a bystander effect. Hum Gene Ther 2000; 11: 285–292.

    Article  CAS  PubMed  Google Scholar 

  84. Kammertoens T, Gelbmann W, Karle P, Alton K, Saller R, Salmons B et al. Combined chemotherapy of murine mammary tumors by local activation of the prodrugs ifosfamide and 5-fluorocytosine. Cancer Gene Ther 2000; 7: 629–636.

    Article  CAS  PubMed  Google Scholar 

  85. Majumdar AS, Zolotorev A, Samuel S, Tran K, Vertin B, Hall-Meier M et al. Efficacy of herpes simplex virus thymidine kinase in combination with cytokine gene therapy in an experimental metastatic breast cancer model. Cancer Gene Ther 2000; 7: 1086–1099.

    Article  CAS  PubMed  Google Scholar 

  86. Vrionis FD, Wu JK, Qi P, Waltzman M, Cherington V, Spray DC . The bystander effect exerted by tumor cells expressing the herpes simplex virus thymidine kinase (HSVtk) gene is dependent on connexin expression and cell communication via gap junctions. Gene Therapy 1997; 4: 577–585.

    Article  CAS  PubMed  Google Scholar 

  87. Ram Z, Walbridge S, Shawker T, Culver KW, Blaese RM, Oldfield EH . The effect of thymidine kinase transduction and ganciclovir therapy on tumor vasculature and growth of 9L gliomas in rats. J Neurosurg 1994; 81: 256–260.

    Article  CAS  PubMed  Google Scholar 

  88. Vile RG, Castleden S, Marshall J, Camplejohn R, Upton C, Chong H . Generation of an anti-tumour immune response in a non-immunogenic tumour: HSVtk killing in vivo stimulates a mononuclear cell infiltrate and a Th1-like profile of intratumoural cytokine expression. Int J Cancer 1997; 71: 267–274.

    Article  CAS  PubMed  Google Scholar 

  89. Gagandeep S, Brew R, Green B, Christmas SE, Klatzmann D, Poston GJ et al. Prodrug-activated gene therapy: involvement of an immunological component in the ‘bystander effect’. Cancer Gene Ther 1996; 3: 83–88.

    CAS  PubMed  Google Scholar 

  90. Chen SH, Chen XH, Wang Y, Kosai K, Finegold MJ, Rich SS et al. Combination gene therapy for liver metastasis of colon carcinoma in vivo. Proc Natl Acad Sci USA 1995; 92: 2577–2581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. O'Malley BW, Cope KA, Chen SH, Li D, Schwarta MR, Woo SL . Combination gene therapy for oral cancer in a murine model. Cancer Res 1996; 56: 1737–1741.

    CAS  PubMed  Google Scholar 

  92. DeFatta RJ, Chervenak RP, De Benedetti A . A cancer gene therapy approach through translational control of a suicide gene. Cancer Gene Ther 2002; 9: 505–512.

    Article  CAS  PubMed  Google Scholar 

  93. Kerekatte V, Smiley K, Hu B, Smith A, Gelder F, De Benedetti A . The proto-oncogene/translation factor eIF4E: a survey of its expression in breast carcinomas. Int J Cancer 1995; 64: 27–31.

    Article  CAS  PubMed  Google Scholar 

  94. Uckert W, Kammertons T, Haack K, Qin Z, Gebert J, Schendel DJ et al. Double suicide gene (cytosine deaminase and herpes simplex virus thymidine kinase) but not single gene transfer allows reliable elimination of tumor cells in vivo. Hum Gene Ther 1998; 9: 855–865.

    Article  CAS  PubMed  Google Scholar 

  95. Pandha HS, Martin LA, Rigg A, Hurst HC, Stamp GW, Sikora K et al. Genetic prodrug activation therapy for breast cancer: a phase I clinical trial of erbB-2-directed suicide gene expression. J Clin Oncol 1999; 17: 2180–2189.

    Article  CAS  PubMed  Google Scholar 

  96. Braybrooke JP, Slade A, Deplanque G, Harrop R, Madhusudan S, Forster MD et al. Phase I study of MetXia-P450 gene therapy and oral cyclophosphamide for patients with advanced breast cancer or melanoma. Clin Cancer Res 2005; 11: 1512–1520.

    Article  CAS  PubMed  Google Scholar 

  97. Bold RJ, Termuhlen PM, McConkey DJ . Apoptosis, cancer and cancer therapy. Surg Oncol 1997; 6: 133–142.

    Article  CAS  PubMed  Google Scholar 

  98. Jaattela M . Escaping cell death: survival proteins in cancer. Exp Cell Res 1999; 248: 30–43.

    Article  CAS  PubMed  Google Scholar 

  99. Hanahan D, Weinberg RA . The hallmarks of cancer. Cell 2000; 100: 57–70.

    Article  CAS  PubMed  Google Scholar 

  100. Nylandsted J, Rohde M, Brand K, Bastholm L, Elling F, Jaattela M . Selective depletion of heat shock protein 70 (Hsp70) activates a tumor-specific death program that is independent of caspases and bypasses Bcl-2. Proc Natl Acad Sci USA 2000; 97: 7871–7876.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Thornberry NA, Lazebnik Y . Caspases: enemies within. Science 1998; 281: 1312–1316.

    Article  CAS  PubMed  Google Scholar 

  102. Vaux DL, Cory S, Adams JM . Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells. Nature 1988; 335: 440–442.

    Article  CAS  PubMed  Google Scholar 

  103. Lin J, Page C, Jin X, Sethi AO, Patel R, Nunez G . Suppression activity of pro-apoptotic gene products in cancer cells, a potential application for cancer gene therapy. Anticancer Res 2001; 21: 831–839.

    CAS  PubMed  Google Scholar 

  104. Ealovega MW, McGinnis PK, Sumantran VN, Clarke MF, Wicha MS . bcl-xs gene therapy induces apoptosis of human mammary tumors in nude mice. Cancer Res 1996; 56: 1965–1969.

    CAS  PubMed  Google Scholar 

  105. Zou Y, Peng H, Zhou B, Wen Y, Wang SC, Tsai EM et al. Systemic tumor suppression by the proapoptotic gene bik. Cancer Res 2002; 62: 8–12.

    CAS  PubMed  Google Scholar 

  106. Tai YT, Strobel T, Kufe D, Cannistra SA . In vivo cytotoxicity of ovarian cancer cells through tumor-selective expression of the BAX gene. Cancer Res 1999; 59: 2121–2126.

    CAS  PubMed  Google Scholar 

  107. Griffith TS, Anderson RD, Davidson BL, Williams RD, Ratliff TL . Adenoviral-mediated transfer of the TNF-related apoptosis-inducing ligand/Apo-2 ligand gene induces tumor cell apoptosis. J Immunol 2000; 165: 2886–2894.

    Article  CAS  PubMed  Google Scholar 

  108. Lin T, Huang X, Gu J, Zhang L, Roth JA, Xiong M et al. Long-term tumor-free survival from treatment with the GFP-TRAIL fusion gene expressed from the hTERT promoter in breast cancer cells. Oncogene 2002; 21: 8020–8028.

    Article  CAS  PubMed  Google Scholar 

  109. Sanlioglu AD, Dirice E, Aydin C, Erin N, Koksoy S, Sanlioglu S . Surface TRAIL decoy receptor-4 expression is correlated with TRAIL resistance in MCF7 breast cancer cells. BMC Cancer 2005; 5: 54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Chinnaiyan AM, O'Rourke K, Tewari M, Dixit VM . FADD, a novel death domain-containing protein, interacts with the death domain of Fas and initiates apoptosis. Cell 1995; 81: 505–512.

    Article  CAS  PubMed  Google Scholar 

  111. Nagata S, Golstein P . The Fas death factor. Science 1995; 267: 1449–1456.

    Article  CAS  PubMed  Google Scholar 

  112. Yonehara S, Ishii A, Yonehara M . A cell-killing monoclonal antibody (anti-Fas) to a cell surface antigen co-downregulated with the receptor of tumor necrosis factor. J Exp Med 1989; 169: 1747–1756.

    Article  CAS  PubMed  Google Scholar 

  113. Boldin MP, Goncharov TM, Goltsev YV, Wallach D . Involvement of MACH, a novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-induced cell death. Cell 1996; 85: 803–815.

    Article  CAS  PubMed  Google Scholar 

  114. Shinoura N, Yamamoto N, Asai A, Kirino T, Hamada H . Adenovirus-mediated transfer of Fas ligand gene augments radiation-induced apoptosis in U-373MG glioma cells. Jpn J Cancer Res 2000; 91: 1044–1050.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Hung MC, Hortobagyi GN, Ueno NT . Development of clinical trial of E1A gene therapy targeting HER-2/neu-overexpressing breast and ovarian cancer. Adv Exp Med Biol 2000; 465: 171–180.

    Article  CAS  PubMed  Google Scholar 

  116. Ueno NT, Bartholomeusz C, Xia W, Anklesaria P, Bruckheimer EM, Mebel E et al. Systemic gene therapy in human xenograft tumor models by liposomal delivery of the E1A gene. Cancer Res 2002; 62: 6712–6716.

    CAS  PubMed  Google Scholar 

  117. Ueno NT, Bartholomeusz C, Herrmann JL, Estrov Z, Shao R, Andreeff M et al. E1A-mediated paclitaxel sensitization in HER-2/neu-overexpressing ovarian cancer SKOV3.ip1 through apoptosis involving the caspase-3 pathway. Clin Cancer Res 2000; 6: 250–259.

    CAS  PubMed  Google Scholar 

  118. Lee EJ, Jakacka M, Duan WR, Chien PY, Martinson F, Gehm BD et al. Adenovirus-directed expression of dominant negative estrogen receptor induces apoptosis in breast cancer cells and regression of tumors in nude mice. Mol Med 2001; 7: 773–782.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Davidoff AM, Nathwani AC . Antiangiogenic gene therapy for cancer treatment. Curr Hematol Rep 2004; 3: 267–273.

    PubMed  Google Scholar 

  120. Voravud N, Charuruk N . Tumor angiogenesis. J Med Assoc Thai 1999; 82: 394–404.

    CAS  PubMed  Google Scholar 

  121. Folkman J, Shing Y . Angiogenesis. J Biol Chem 1992; 267: 10931–10934.

    CAS  PubMed  Google Scholar 

  122. Chen QR, Kumar D, Stass SA, Mixson AJ . Liposomes complexed to plasmids encoding angiostatin and endostatin inhibit breast cancer in nude mice. Cancer Res 1999; 59: 3308–3312.

    CAS  PubMed  Google Scholar 

  123. Oga M, Takenaga K, Sato Y, Nakajima H, Koshikawa N, Osato K et al. Inhibition of metastatic brain tumor growth by intramuscular administration of the endostatin gene. Int J Oncol 2003; 23: 73–79.

    CAS  PubMed  Google Scholar 

  124. Sacco MG, Soldati S, Mira Cato E, Cattaneo L, Pratesi G, Scanziani E et al. Combined effects on tumor growth and metastasis by anti-estrogenic and antiangiogenic therapies in MMTV-neu mice. Gene Therapy 2002; 9: 1338–1341.

    Article  CAS  PubMed  Google Scholar 

  125. Wu Z, O'Reilly MS, Folkman J, Shing Y . Suppression of tumor growth with recombinant murine angiostatin. Biochem Biophys Res Commun 1997; 236: 651–654.

    Article  CAS  PubMed  Google Scholar 

  126. Sim BK, O'Reilly MS, Liang H, Fortier AH, He W, Madsen JW et al. A recombinant human angiostatin protein inhibits experimental primary and metastatic cancer. Cancer Res 1997; 57: 1329–1334.

    CAS  PubMed  Google Scholar 

  127. Coley WB . The treatment of malignant tumors by repeated inoculations of erysipelas. With a report of ten original cases, 1893. Clin Orthop Relat Res 1991; 262: 3–11.

    Google Scholar 

  128. Strong TV . Gene therapy for carcinoma of the breast: genetic immunotherapy. Breast Cancer Res 2000; 2: 15–21.

    Article  CAS  PubMed  Google Scholar 

  129. Siegel JP, Puri RK . Interleukin-2 toxicity. J Clin Oncol 1991; 9: 694–704.

    Article  CAS  PubMed  Google Scholar 

  130. Coveney E, Clary B, Iacobucci M, Philip R, Lyerly K . Active immunotherapy with transiently transfected cytokine-secreting tumor cells inhibits breast cancer metastases in tumor-bearing animals. Surgery 1996; 120: 265–272; discussion 272–263.

    Article  CAS  PubMed  Google Scholar 

  131. Gansbacher B, Zier K, Daniels B, Cronin K, Bannerji R, Gilboa E . Interleukin 2 gene transfer into tumor cells abrogates tumorigenicity and induces protective immunity. J Exp Med 1990; 172: 1217–1224.

    Article  CAS  PubMed  Google Scholar 

  132. Haddada H, Ragot T, Cordier L, Duffour MT, Perricaudet M . Adenoviral interleukin-2 gene transfer into P815 tumor cells abrogates tumorigenicity and induces antitumoral immunity in mice. Hum Gene Ther 1993; 4: 703–711.

    Article  CAS  PubMed  Google Scholar 

  133. Bubenik J, Voitenok NN, Kieler J, Prassolov VS, Chumakov PM, Bubenikova D et al. Local administration of cells containing an inserted IL-2 gene and producing IL-2 inhibits growth of human tumors in nu/nu mice. Immunol Lett 1988; 19: 279–282.

    Article  CAS  PubMed  Google Scholar 

  134. Lichtor T, Glick RP, Lin H, I OS, Cohen EP . Intratumoral injection of IL-secreting syngeneic/allogeneic fibroblasts transfected with DNA from breast cancer cells prolongs the survival of mice with intracerebral breast cancer. Cancer Gene Ther 2005; 12: 708–714.

    Article  CAS  PubMed  Google Scholar 

  135. Slos P, De Meyer M, Leroy P, Rousseau C, Acres B . Immunotherapy of established tumors in mice by intratumoral injection of an adenovirus vector harboring the human IL-2 cDNA: induction of CD8(+) T-cell immunity and NK activity. Cancer Gene Ther 2001; 8: 321–332.

    Article  CAS  PubMed  Google Scholar 

  136. Yu JS, Wei MX, Chiocca EA, Martuza RL, Tepper RI . Treatment of glioma by engineered interleukin 4-secreting cells. Cancer Res 1993; 53: 3125–3128.

    CAS  PubMed  Google Scholar 

  137. Zitvogel L, Tahara H, Robbins PD, Storkus WJ, Clarke MR, Nalesnik MA et al. Cancer immunotherapy of established tumors with IL-12. Effective delivery by genetically engineered fibroblasts. J Immunol 1995; 155: 1393–1403.

    CAS  PubMed  Google Scholar 

  138. Osaki T, Hashimoto W, Gambotto A, Okamura H, Robbins PD, Kurimoto M et al. Potent antitumor effects mediated by local expression of the mature form of the interferon-gamma inducing factor, interleukin-18 (IL-18). Gene Therapy 1999; 6: 808–815.

    Article  CAS  PubMed  Google Scholar 

  139. Lo CH, Lee SC, Wu PY, Pan WY, Su J, Cheng CW et al. Antitumor and antimetastatic activity of IL-23. J Immunol 2003; 171: 600–607.

    Article  CAS  PubMed  Google Scholar 

  140. Hui K, Grosveld F, Festenstein H . Rejection of transplantable AKR leukaemia cells following MHC DNA-mediated cell transformation. Nature 1984; 311: 750–752.

    Article  CAS  PubMed  Google Scholar 

  141. Wallich R, Bulbuc N, Hammerling GJ, Katzav S, Segal S, Feldman M . Abrogation of metastatic properties of tumour cells by de novo expression of H-2K antigens following H-2 gene transfection. Nature 1985; 315: 301–305.

    Article  CAS  PubMed  Google Scholar 

  142. Ruppert JM, Wright M, Rosenfeld M, Grushcow J, Bilbao G, Curiel DT et al. Gene therapy strategies for carcinoma of the breast. Breast Cancer Res Treat 1997; 44: 93–114.

    Article  CAS  PubMed  Google Scholar 

  143. Tanaka K, Isselbacher KJ, Khoury G, Jay G . Reversal of oncogenesis by the expression of a major histocompatibility complex class I gene. Science 1985; 228: 26–30.

    Article  CAS  PubMed  Google Scholar 

  144. Knuth A, Wolfel T, Meyer zum Buschenfelde KH . Cellular and humoral immune responses against cancer: implications for cancer vaccines. Curr Opin Immunol 1991; 3: 659–664.

    Article  CAS  PubMed  Google Scholar 

  145. Wolfel T, Klehmann E, Muller C, Schutt KH, Meyer zum Buschenfelde KH, Knuth A . Lysis of human melanoma cells by autologous cytolytic T cell clones. Identification of human histocompatibility leukocyte antigen A2 as a restriction element for three different antigens. J Exp Med 1989; 170: 797–810.

    Article  CAS  PubMed  Google Scholar 

  146. Knuth A, Wolfel T, Klehmann E, Boon T, Meyer zum Buschenfelde KH . Cytolytic T-cell clones against an autologous human melanoma: specificity study and definition of three antigens by immunoselection. Proc Natl Acad Sci USA 1989; 86: 2804–2808.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  147. Yip YL, Ward RL . Anti-ErbB-2 monoclonal antibodies and ErbB-2-directed vaccines. Cancer Immunol Immunother 2002; 50: 569–587.

    Article  CAS  PubMed  Google Scholar 

  148. Kawashima I, Tsai V, Southwood S, Takesako K, Sette A, Celis E . Identification of HLA-A3-restricted cytotoxic T lymphocyte epitopes from carcinoembryonic antigen and HER-2/neu by primary in vitro immunization with peptide-pulsed dendritic cells. Cancer Res 1999; 59: 431–435.

    CAS  PubMed  Google Scholar 

  149. Toso JF, Oei C, Oshidari F, Tartaglia J, Paoletti E, Lyerly HK et al. MAGE-1-specific precursor cytotoxic T-lymphocytes present among tumor-infiltrating lymphocytes from a patient with breast cancer: characterization and antigen-specific activation. Cancer Res 1996; 56: 16–20.

    CAS  PubMed  Google Scholar 

  150. Ioannides CG, Fisk B, Jerome KR, Irimura T, Wharton JT, Finn OJ . Cytotoxic T cells from ovarian malignant tumors can recognize polymorphic epithelial mucin core peptides. J Immunol 1993; 151: 3693–3703.

    CAS  PubMed  Google Scholar 

  151. Vonderheide RH, Hahn WC, Schultze JL, Nadler LM . The telomerase catalytic subunit is a widely expressed tumor-associated antigen recognized by cytotoxic T lymphocytes. Immunity 1999; 10: 673–679.

    Article  CAS  PubMed  Google Scholar 

  152. Kustikova O, Kramerov D, Grigorian M, Berezin V, Bock E, Lukanidin E et al. Fra-1 induces morphological transformation and increases in vitro invasiveness and motility of epithelioid adenocarcinoma cells. Mol Cell Biol 1998; 18: 7095–7105.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Luo Y, Zhou H, Mizutani M, Mizutani N, Liu C, Xiang R et al. A DNA vaccine targeting Fos-related antigen 1 enhanced by IL-18 induces long-lived T-cell memory against tumor recurrence. Cancer Res 2005; 65: 3419–3427.

    Article  CAS  PubMed  Google Scholar 

  154. Tang Y, Nakada MT, Kesavan P, McCabe F, Millar H, Rafferty P et al. Extracellular matrix metalloproteinase inducer stimulates tumor angiogenesis by elevating vascular endothelial cell growth factor and matrix metalloproteinases. Cancer Res 2005; 65: 3193–3199.

    Article  CAS  PubMed  Google Scholar 

  155. Salceda S, Tang T, Kmet M, Munteanu A, Ghosh M, Macina R et al. The immunomodulatory protein B7-H4 is overexpressed in breast and ovarian cancers and promotes epithelial cell transformation. Exp Cell Res 2005; 306: 128–141.

    Article  CAS  PubMed  Google Scholar 

  156. Tringler B, Zhuo S, Pilkington G, Torkko KC, Singh M, Lucia MS et al. B7-h4 is highly expressed in ductal and lobular breast cancer. Clin Cancer Res 2005; 11: 1842–1848.

    Article  CAS  PubMed  Google Scholar 

  157. Chang SY, Lee KC, Ko SY, Ko HJ, Kang CY . Enhanced efficacy of DNA vaccination against Her-2/neu tumor antigen by genetic adjuvants. Int J Cancer 2004; 111: 86–95.

    Article  CAS  PubMed  Google Scholar 

  158. von Mehren M, Arlen P, Gulley J, Rogatko A, Cooper HS, Meropol NJ et al. The influence of granulocyte macrophage colony-stimulating factor and prior chemotherapy on the immunological response to a vaccine (ALVAC-CEA B7.1) in patients with metastatic carcinoma. Clin Cancer Res 2001; 7: 1181–1191.

    CAS  PubMed  Google Scholar 

  159. Sakai Y, Morrison BJ, Burke JD, Park JM, Terabe M, Janik JE et al. Vaccination by genetically modified dendritic cells expressing a truncated neu oncogene prevents development of breast cancer in transgenic mice. Cancer Res 2004; 64: 8022–8028.

    Article  CAS  PubMed  Google Scholar 

  160. Banchereau J, Steinman RM . Dendritic cells and the control of immunity. Nature 1998; 392: 245–252.

    Article  CAS  PubMed  Google Scholar 

  161. Thery C, Amigorena S . The cell biology of antigen presentation in dendritic cells. Curr Opin Immunol 2001; 13: 45–51.

    Article  CAS  PubMed  Google Scholar 

  162. Gabrilovich DI, Nadaf S, Corak J, Berzofsky JA, Carbone DP . Dendritic cells in antitumor immune responses. II. Dendritic cells grown from bone marrow precursors, but not mature DC from tumor-bearing mice, are effective antigen carriers in the therapy of established tumors. Cell Immunol 1996; 170: 111–119.

    Article  CAS  PubMed  Google Scholar 

  163. Disis ML, Gooley TA, Rinn K, Davis D, Piepkorn M, Cheever MA et al. Generation of T-cell immunity to the HER-2/neu protein after active immunization with HER-2/neu peptide-based vaccines. J Clin Oncol 2002; 20: 2624–2632.

    Article  CAS  PubMed  Google Scholar 

  164. Panelli MC, Wunderlich J, Jeffries J, Wang E, Mixon A, Rosenberg SA et al. Phase 1 study in patients with metastatic melanoma of immunization with dendritic cells presenting epitopes derived from the melanoma-associated antigens MART-1 and gp100. J Immunother 2000; 23: 487–498.

    Article  CAS  PubMed  Google Scholar 

  165. Timmerman JM, Czerwinski DK, Davis TA, Hsu FJ, Benike C, Hao ZM et al. Idiotype-pulsed dendritic cell vaccination for B-cell lymphoma: clinical and immune responses in 35 patients. Blood 2002; 99: 1517–1526.

    Article  CAS  PubMed  Google Scholar 

  166. Viehl CT, Becker-Hapak M, Lewis JS, Tanaka Y, Liyanage UK, Linehan DC et al. A tat fusion protein-based tumor vaccine for breast cancer. Ann Surg Oncol 2005; 12: 517–525.

    Article  PubMed  Google Scholar 

  167. Viehl CT, Tanaka Y, Chen T, Frey DM, Tran A, Fleming TP et al. Tat mammaglobin fusion protein transduced dendritic cells stimulate mammaglobin-specific CD4 and CD8 T cells. Breast Cancer Res Treat 2005; 91: 271–278.

    Article  CAS  PubMed  Google Scholar 

  168. Hudson PJ . Recombinant antibodies: a novel approach to cancer diagnosis and therapy. Expert Opin Investig Drugs 2000; 9: 1231–1242.

    Article  CAS  PubMed  Google Scholar 

  169. Larin SS, Georgiev GP, Kiselev SL . Gene transfer approaches in cancer immunotherapy. Gene Therapy 2004; 11 (Suppl 1): S18–S25.

    Article  CAS  PubMed  Google Scholar 

  170. Staud F, Pavek P . Breast cancer resistance protein (BCRP/ABCG2). Int J Biochem Cell Biol 2005; 37: 720–725.

    Article  CAS  PubMed  Google Scholar 

  171. Pavek P, Merino G, Wagenaar E, Bolscher E, Novotna M, Jonker JW et al. Human breast cancer resistance protein: interactions with steroid drugs, hormones, the dietary carcinogen 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine, and transport of cimetidine. J Pharmacol Exp Ther 2005; 312: 144–152.

    Article  CAS  PubMed  Google Scholar 

  172. Lebedeva S, Bagdasarova S, Tyler T, Mu X, Wilson DR, Gjerset RA . Tumor suppression and therapy sensitization of localized and metastatic breast cancer by adenovirus p53. Hum Gene Ther 2001; 12: 763–772.

    Article  CAS  PubMed  Google Scholar 

  173. Pruschy M, Rocha S, Zaugg K, Tenzer A, Hess C, Fisher DE et al. Key targets for the execution of radiation-induced tumor cell apoptosis: the role of p53 and caspases. Int J Radiat Oncol Biol Phys 2001; 49: 561–567.

    Article  CAS  PubMed  Google Scholar 

  174. Dasika GK, Lin SC, Zhao S, Sung P, Tomkinson A, Lee EY . DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis. Oncogene 1999; 18: 7883–7899.

    Article  CAS  PubMed  Google Scholar 

  175. Macleod KF, Sherry N, Hannon G, Beach D, Tokino T, Kinzler K et al. p53-dependent and independent expression of p21 during cell growth, differentiation, and DNA damage. Genes Dev 1995; 9: 935–944.

    Article  CAS  PubMed  Google Scholar 

  176. Szumiel I . Ionizing radiation-induced cell death. Int J Radiat Biol 1994; 66: 329–341.

    Article  CAS  PubMed  Google Scholar 

  177. Spitz FR, Nguyen D, Skibber JM, Meyn RE, Cristiano RJ, Roth JA . Adenoviral-mediated wild-type p53 gene expression sensitizes colorectal cancer cells to ionizing radiation. Clin Cancer Res 1996; 2: 1665–1671.

    CAS  PubMed  Google Scholar 

  178. Jasty R, Lu J, Irwin T, Suchard S, Clarke MF, Castle VP . Role of p53 in the regulation of irradiation-induced apoptosis in neuroblastoma cells. Mol Genet Metab 1998; 65: 155–164.

    Article  CAS  PubMed  Google Scholar 

  179. Sakakura C, Sweeney EA, Shirahama T, Igarashi Y, Hakomori S, Nakatani H et al. Overexpression of bax sensitizes human breast cancer MCF-7 cells to radiation-induced apoptosis. Int J Cancer 1996; 67: 101–105.

    Article  CAS  PubMed  Google Scholar 

  180. Broaddus WC, Liu Y, Steele LL, Gillies GT, Lin PS, Loudon WG et al. Enhanced radiosensitivity of malignant glioma cells after adenoviral p53 transduction. J Neurosurg 1999; 91: 997–1004.

    Article  CAS  PubMed  Google Scholar 

  181. Sartor CI . Biological modifiers as potential radiosensitizers: targeting the epidermal growth factor receptor family. Semin Oncol 2000; 27: 15–20; discussion 92–100.

    CAS  PubMed  Google Scholar 

  182. Lammering G, Lin PS, Contessa JN, Hampton JL, Valerie K, Schmidt-Ullrich RK . Adenovirus-mediated overexpression of dominant negative epidermal growth factor receptor-CD533 as a gene therapeutic approach radiosensitizes human carcinoma and malignant glioma cells. Int J Radiat Oncol Biol Phys 2001; 51: 775–784.

    Article  CAS  PubMed  Google Scholar 

  183. Lammering G, Hewit TH, Hawkins WT, Contessa JN, Reardon DB, Lin PS et al. Epidermal growth factor receptor as a genetic therapy target for carcinoma cell radiosensitization. J Natl Cancer Inst 2001; 93: 921–929.

    Article  CAS  PubMed  Google Scholar 

  184. Lammering G, Valerie K, Lin PS, Mikkelsen RB, Contessa JN, Feden JP et al. Radiosensitization of malignant glioma cells through overexpression of dominant-negative epidermal growth factor receptor. Clin Cancer Res 2001; 7: 682–690.

    CAS  PubMed  Google Scholar 

  185. Wang H, Nan L, Yu D, Agrawal S, Zhang R . Antisense anti-MDM2 oligonucleotides as a novel therapeutic approach to human breast cancer: in vitro and in vivo activities and mechanisms. Clin Cancer Res 2001; 7: 3613–3624.

    CAS  PubMed  Google Scholar 

  186. Ciardiello F, Caputo R, Troiani T, Borriello G, Kandimalla ER, Agrawal S et al. Antisense oligonucleotides targeting the epidermal growth factor receptor inhibit proliferation, induce apoptosis, and cooperate with cytotoxic drugs in human cancer cell lines. Int J Cancer 2001; 93: 172–178.

    Article  CAS  PubMed  Google Scholar 

  187. Geiger T, Muller M, Dean NM, Fabbro D . Antitumor activity of a PKC-alpha antisense oligonucleotide in combination with standard chemotherapeutic agents against various human tumors transplanted into nude mice. Anticancer Drug Des 1998; 13: 35–45.

    CAS  PubMed  Google Scholar 

  188. Lopes de Menezes DE, Hudon N, McIntosh N, Mayer LD . Molecular and pharmacokinetic properties associated with the therapeutics of bcl-2 antisense oligonucleotide G3139 combined with free and liposomal doxorubicin. Clin Cancer Res 2000; 6: 2891–2902.

    CAS  PubMed  Google Scholar 

  189. Adjei AA, Dy GK, Erlichman C, Reid JM, Sloan JA, Pitot HC et al. A phase I trial of ISIS 2503, an antisense inhibitor of H-ras, in combination with gemcitabine in patients with advanced cancer. Clin Cancer Res 2003; 9: 115–123.

    CAS  PubMed  Google Scholar 

  190. Marshall J, Chen H, Yang D, Figueira M, Bouker KB, Ling Y et al. A phase I trial of a Bcl-2 antisense (G3139) and weekly docetaxel in patients with advanced breast cancer and other solid tumors. Ann Oncol 2004; 15: 1274–1283.

    Article  CAS  PubMed  Google Scholar 

  191. Sakakura C, Sweeney EA, Shirahama T, Igarashi Y, Hakomori S, Tsujimoto H et al. Overexpression of bax enhances the radiation sensitivity in human breast cancer cells. Surg Today 1997; 27: 90–93.

    Article  CAS  PubMed  Google Scholar 

  192. Sakakura C, Sweeney EA, Shirahama T, Igarashi Y, Hakomori S, Tsujimoto H et al. Overexpression of bax sensitizes breast cancer MCF-7 cells to cisplatin and etoposide. Surg Today 1997; 27: 676–679.

    Article  CAS  PubMed  Google Scholar 

  193. Kobayashi H, Takemura Y, Miyachi H . Novel approaches to reversing anti-cancer drug resistance using gene-specific therapeutics. Hum Cell 2001; 14: 172–184.

    CAS  PubMed  Google Scholar 

  194. Kim SH, Kim JH, Kolozsvary A, Brown SL, Freytag SO . Preferential radiosensitization of 9L glioma cells transduced with HSV-tk gene by acyclovir. J Neurooncol 1997; 33: 189–194.

    Article  CAS  PubMed  Google Scholar 

  195. Atkinson G, Hall SJ . Prodrug activation gene therapy and external beam irradiation in the treatment of prostate cancer. Urology 1999; 54: 1098–1104.

    Article  CAS  PubMed  Google Scholar 

  196. Chhikara M, Huang H, Vlachaki MT, Zhu X, Teh B, Chiu KJ et al. Enhanced therapeutic effect of HSV-tk+GCV gene therapy and ionizing radiation for prostate cancer. Mol Ther 2001; 3: 536–542.

    Article  CAS  PubMed  Google Scholar 

  197. Vlachaki MT, Chhikara M, Aguilar L, Zhu X, Chiu KJ, Woo S et al. Enhanced therapeutic effect of multiple injections of HSV-TK+GCV gene therapy in combination with ionizing radiation in a mouse mammary tumor model. Int J Radiat Oncol Biol Phys 2001; 51: 1008–1017.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by Grant of the Deutsche Forschungsgemeinschaft Sto 647/1-1 (to MA Stoff-Khalili), grants from the National Institutes of Health: RO1CA08382-05A1, RO1CA111569-01A1, and Department of Defense: W81XWH-05-1-0035 (to DT Curiel). Dr M Everts is thanked for critically reading the manuscript.

Author information

Authors and Affiliations

  1. Division of Human Gene Therapy, Departments of Medicine, Surgery, Pathology and the Gene Therapy Center, University of Alabama at Birmingham, Birminham, AL, USA

    M A Stoff-Khalili & D T Curiel

  2. Department of Obstetrics and Gynecology, University of Duesseldorf, Medical Center, Duesseldorf, Germany

    M A Stoff-Khalili & P Dall

Authors
  1. M A Stoff-Khalili
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P Dall
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. D T Curiel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D T Curiel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stoff-Khalili, M., Dall, P. & Curiel, D. Gene therapy for carcinoma of the breast. Cancer Gene Ther 13, 633–647 (2006). https://doi.org/10.1038/sj.cgt.7700929

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.cgt.7700929

Keywords

This article is cited by

Search

Advanced search

Quick links