Etracker Debug:
	et_pagename = "Radiology and Oncology|raon|C|[EN]"
	
        
Jump to ContentJump to Main Navigation

Radiology and Oncology

The Journal of Association of Radiology and Oncology

4 Issues per year

IMPACT FACTOR increased in 2013: 1.667

Open Access
VolumeIssuePage

Open Access

Targeted gene therapy in radiotherapy

Urska Kamensek1 / Gregor Sersa1

Department of Experimental Oncology, Institute of Oncology Ljubljana, Slovenia1

This content is open access.

Citation Information: Radiology and Oncology. Volume 42, Issue 3, Pages 115–135, ISSN (Online) 1581-3207, ISSN (Print) 1318-2099, DOI: 10.2478/v10019-008-0009-1, September 2008

Publication History

Published Online:
2008-09-08

Targeted gene therapy in radiotherapy

The dramatic pace in development of gene therapy over the past decades has made it a realistic alternative for the treatment of cancer. Radiotherapy, on the other hand, is one of the most commonly used and well established cancer treatment modalities. The latest improvements in the physical targeting ability of radiotherapy and understanding of the molecular mechanism involved in the cellular response to ionizing radiation have presented an opportunity to combine radiotherapy with gene therapy. This review article will focus on gene therapy strategies that can be used to enhance the effectiveness of radiotherapy, with an emphasis on transcriptional targeting approaches.

Keywords: gene therapy; radiotherapy; transcriptional targeting

  • Mundt AJ, Vijayakumar S, Nemunaitis J, Sandler A, Schwartz H, Hanna N, Peabody T, Senzer N, Chu K, Rasmussen CS, Kessler PD, Rasmussen HS, Warso M, Kufe DW, Gupta TD, Weichselbaum RR. A Phase I trial of TNFerade biologic in patients with soft tissue sarcoma in the extremities. Clin Cancer Res 2004; 10(17): 5747-53. [PubMed] [CrossRef]

  • Manome Y, Kunieda T, Wen PY, Koga T, Kufe DW, Ohno T. Transgene expression in malignant glioma using a replication-defective adenoviral vector containing the Egr-1 promoter: activation by ionizing radiation or uptake of radioactive iododeoxyuridine. Hum Gene Ther 1998; 9(10): 1409-17. [PubMed]

  • Weichselbaum RR, Hallahan DE, Beckett MA, Mauceri HJ, Lee H, Sukhatme VP, Kufe DW. Gene therapy targeted by radiation preferentially radiosensitizes tumor cells. Cancer Res 1994; 54(16): 4266-9. [PubMed]

  • Hallahan DE, Mauceri HJ, Seung LP, Dunphy EJ, Wayne JD, Hanna NN, Toledano A, Hellman S, Kufe DW, Weichselbaum RR. Spatial and temporal control of gene therapy using ionizing radiation. Nat Med 1995; 1(8): 786-91. [CrossRef] [PubMed]

  • Chung TD, Mauceri HJ, Hallahan DE, Yu JJ, Chung S, Grdina WL, Yajnik S, Kufe DW, Weichselbaum RR. Tumor necrosis factor-alpha-based gene therapy enhances radiation cytotoxicity in human prostate cancer. Cancer Gene Ther 1998; 5(6): 344-9. [PubMed]

  • Gupta VK, Park JO, Jaskowiak NT, Mauceri HJ, Seetharam S, Weichselbaum RR, Posner MC. Combined gene therapy and ionizing radiation is a novel approach to treat human esophageal adenocarcinoma. Ann Surg Oncol 2002; 9(5): 500-4. [CrossRef] [PubMed]

  • Weichselbaum RR, Kufe DW, Hellman S, Rasmussen HS, King CR, Fischer PH, Mauceri HJ. Radiation-induced tumour necrosis factor-alpha expression: clinical application of transcriptional and physical targeting of gene therapy. Lancet Oncol 2002; 3(11): 665-71. [PubMed] [CrossRef]

  • Rasmussen H, Rasmussen C, Lempicki M, Durham R, Brough D, King CR, Weichselbaum R. TNFerade Biologic: preclinical toxicology of a novel adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor alpha gene. Cancer Gene Ther 2002; 9(11): 951-7. [CrossRef] [PubMed]

  • Senzer N, Mani S, Rosemurgy A, Nemunaitis J, Cunningham C, Guha C, Bayol N, Gillen M, Chu K, Rasmussen C, Rasmussen H, Kufe D, Weichselbaum R, Hanna N. TNFerade biologic, an adenovector with a radiation-inducible promoter, carrying the human tumor necrosis factor alpha gene: a phase I study in patients with solid tumors. J Clin Oncol 2004; 22(4): 592-601. [CrossRef] [PubMed]

  • Salloum RM, Saunders MP, Mauceri HJ, Hanna NN, Gorski DH, Posner MC, Stratford IJ, Weichselbaum RR. Dual induction of the Epo-Egr-TNF-alpha-plasmid in hypoxic human colon adenocarcinoma produces tumor growth delay. Am Surg 2003; 69(1): 24-7. [PubMed]

  • Scott SD, Marples B, Hendry JH, Lashford LS, Embleton MJ, Hunter RD, Howell A, Margison GP. A radiation-controlled molecular switch for use in gene therapy of cancer. Gene Ther 2000; 7(13): 1121-5. [PubMed] [CrossRef]

  • Bernier J, Hall EJ, Giaccia A. Radiation oncology: a century of achievements. Nat Rev Cancer 2004; 4(9): 737-47. [PubMed] [CrossRef]

  • Tubiana M, Eschwege F. Conformal radiotherapy and intensity-modulated radiotherapy-clinical data. Acta Oncol 2000; 39(5): 555-67. [PubMed]

  • Shinohara ET, Lu B, Hallahan DE. The use of gene therapy in cancer research and treatment. Technol Cancer Res Treat 2004; 3(5): 479-90.

  • Gridley DS, Slater JM. Combining gene therapy and radiation against cancer. Curr Gene Ther 2004; 4(3): 231-48. [CrossRef] [PubMed]

  • Robson T, Worthington J, McKeown SR, Hirst DG. Radiogenic therapy: novel approaches for enhancing tumor radiosensitivity. Technol Cancer Res Treat 2005; 4(4): 343-61. [PubMed]

  • Lumniczky K, Safrany G. Cancer gene therapy: combination with radiation therapy and the role of bystander cell killing in the anti-tumor effect. Pathol Oncol Res 2006; 12(2): 118-24. [CrossRef] [PubMed]

  • Stevens CW, Zeng M, Cerniglia GJ. Ionizing radiation greatly improves gene transfer efficiency in mammalian cells. Hum Gene Ther 1996; 7(14): 1727-34. [PubMed] [CrossRef]

  • Zeng M, Cerniglia GJ, Eck SL, Stevens CW. High-efficiency stable gene transfer of adenovirus into mammalian cells using ionizing radiation. Hum Gene Ther 1997; 8(9): 1025-32. [PubMed] [CrossRef]

  • Sonveaux P, Dessy C, Brouet A, Jordan BF, Gregoire V, Gallez B, Balligand JL, Feron O. Modulation of the tumor vasculature functionality by ionizing radiation accounts for tumor radiosensitization and promotes gene delivery. FASEB J 2002; 16(14): 1979-81. [PubMed]

  • Weichselbaum RR, Hallahan DE, Sukhatme VP, Kufe DW. Gene therapy targeted by ionizing radiation. Int J Radiat Oncol Biol Phys 1992; 24(3): 565-7. [PubMed] [CrossRef]

  • Sersa G, Miklavcic D, Rudolf Z, Cemazar M, Pucihar G, Snoj M. Electrochemotherapy in treatment of tumours. EJSO 2008; 34(2): 232-240. [CrossRef]

  • Wardman P. Chemical radiosensitizers for use in radiotherapy. Clin Oncol (R Coll Radiol) 2007; 19(6): 397-417. [CrossRef]

  • Kufe D, Weichselbaum R. Radiation therapy: activation for gene transcription and the development of genetic radiotherapy-therapeutic strategies in oncology. Cancer Biol Ther 2003; 2(4): 326-9. [PubMed]

  • Greco O, Dachs GU. Gene directed enzyme/prodrug therapy of cancer: historical appraisal and future prospectives. J Cell Physiol 2001; 187(1): 22-36. [PubMed] [CrossRef]

  • Dachs GU, Tupper J, Tozer GM. From bench to bedside for gene-directed enzyme prodrug therapy of cancer. Anticancer Drugs 2005; 16(4): 349-59. [CrossRef] [PubMed]

  • McKeown SR, Ward C, Robson T. Gene-directed enzyme prodrug therapy: a current assessment. Curr Opin Mol Ther 2004; 6(4): 421-35. [PubMed]

  • Greco O, Marples B, Dachs GU, Williams KJ, Patterson AV, Scott SD. Novel chimeric gene promoters responsive to hypoxia and ionizing radiation. Gene Ther 2002; 9(20): 1403-11. [PubMed] [CrossRef]

  • Khil MS, Kim JH, Mullen CA, Kim SH, Freytag SO. Radiosensitization by 5-fluorocytosine of human colorectal carcinoma cells in culture transduced with cytosine deaminase gene. Clin Cancer Res 1996; 2(1): 53-7. [PubMed]

  • Rogulski KR, Zhang K, Kolozsvary A, Kim JH, Freytag SO. Pronounced antitumor effects and tumor radiosensitization of double suicide gene therapy. Clin Cancer Res 1997; 3(11): 2081-8. [PubMed]

  • Xia K, Liang D, Tang A, Feng Y, Zhang J, Pan Q, Long Z, Dai H, Cai F, Wu L, Zhao S, Chen Z, Xia J. A novel fusion suicide gene yeast CDglyTK plays a role in radio-gene therapy of nasopharyngeal carcinoma. Cancer Gene Ther 2004; 11(12): 790-6. [CrossRef] [PubMed]

  • Freytag SO, Paielli D, Wing M, Rogulski K, Brown S, Kolozsvary A, Seely J, Barton K, Dragovic A, Kim JH. Efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in combination with radiation therapy in an orthotopic mouse prostate cancer model. Int J Radiat Oncol Biol Phys 2002; 54(3): 873-85. [CrossRef]

  • Freytag SO, Khil M, Stricker H, Peabody J, Menon M, Peralta-Venturina M, Nafziger D, Pegg J, Paielli D, Brown S, Barton K, Lu M, guilar-Cordova E, Kim JH. Phase I study of replication-competent adenovirus-mediated double suicide gene therapy for the treatment of locally recurrent prostate cancer. Cancer Res 2002; 62(17): 4968-76. [PubMed]

  • Mitchell JB, Wink DA, DeGraff W, Gamson J, Keefer LK, Krishna MC. Hypoxic mammalian cell radiosensitization by nitric oxide. Cancer Res 1993; 53(24): 5845-8. [PubMed]

  • Kurimoto M, Endo S, Hirashima Y, Hamada H, Ogiichi T, Takaku A. Growth inhibition and radiosensitization of cultured glioma cells by nitric oxide generating agents. J Neurooncol 1999; 42(1): 35-44. [PubMed] [CrossRef]

  • Wang Z, Cook T, Alber S, Liu K, Kovesdi I, Watkins SK, Vodovotz Y, Billiar TR, Blumberg D. Adenoviral gene transfer of the human inducible nitric oxide synthase gene enhances the radiation response of human colorectal cancer associated with alterations in tumor vascularity. Cancer Res 2004; 64(4): 1386-95. [CrossRef] [PubMed]

  • Jordan BF, Misson P, Demeure R, Baudelet C, Beghein N, Gallez B. Changes in tumor oxygenation/perfusion induced by the no donor, isosorbide dinitrate, in comparison with carbogen: monitoring by EPR and MRI. Int J Radiat Oncol Biol Phys 2000; 48(2): 565-70. [PubMed] [CrossRef]

  • Worthington J, Robson T, O'Keeffe M, Hirst DG. Tumour cell radiosensitization using constitutive (CMV) and radiation inducible (WAF1) promoters to drive the iNOS gene: a novel suicide gene therapy. Gene Ther 2002; 9(4): 263-9. [CrossRef]

  • Xie K, Huang S, Dong Z, Juang SH, Gutman M, Xie QW, Nathan C, Fidler IJ. Transfection with the inducible nitric oxide synthase gene suppresses tumorigenicity and abrogates metastasis by K-1735 murine melanoma cells. J Exp Med 1995; 181(4): 1333-43. [CrossRef] [PubMed]

  • Worthington J, McCarthy HO, Barrett E, Adams C, Robson T, Hirst DG. Use of the radiation-inducible WAF1 promoter to drive iNOS gene therapy as a novel anti-cancer treatment. J Gene Med 2004; 6(6): 673-80. [CrossRef]

  • Worthington J, Robson T, Scott S, Hirst D. Evaluation of a synthetic CArG promoter for nitric oxide synthase gene therapy of cancer. Gene Ther 2005; 12(19): 1417-23. [PubMed] [CrossRef]

  • Cook T, Wang Z, Alber S, Liu K, Watkins SC, Vodovotz Y, Billiar TR, Blumberg D. Nitric oxide and ionizing radiation synergistically promote apoptosis and growth inhibition of cancer by activating p53. Cancer Res 2004; 64(21): 8015-21. [CrossRef]

  • Tangney M, Casey G, Larkin JO, Collins CG, Soden D, Cashman J, Whelan MC, O'Sullivan GC. Non-viral in vivo immune gene therapy of cancer: combined strategies for treatment of systemic disease. Cancer Immunol Immunother 2006; 55(11): 1443-50. [CrossRef] [PubMed]

  • Friedman EJ. Immune modulation by ionizing radiation and its implications for cancer immunotherapy. Curr Pharm Des 2002; 8(19): 1765-80. [PubMed] [CrossRef]

  • Demaria S, Bhardwaj N, McBride WH, Formenti SC. Combining radiotherapy and immunotherapy: a revived partnership. Int J Radiat Oncol Biol Phys 2005; 63(3): 655-66. [CrossRef] [PubMed]

  • Tuting T, Storkus WJ, Lotze MT. Gene-based strategies for the immunotherapy of cancer. J Mol Med 1997; 75(7): 478-91. [PubMed]

  • Li CY, Huang Q, Kung HF. Cytokine and immuno-gene therapy for solid tumors. Cell Mol Immunol 2005; 2(2): 81-91. [PubMed]

  • Ulmer JB, Donnelly JJ, Liu MA. Toward the development of DNA vaccines. Curr Opin Biotechnol 1996; 7(6): 653-8. [PubMed] [CrossRef]

  • Stevenson FK, Ottensmeier CH, Johnson P, Zhu D, Buchan SL, McCann KJ, Roddick JS, King AT, McNicholl F, Savelyeva N, Rice J. DNA vaccines to attack cancer. Proc Natl Acad Sci U S A 2004; 101(2): 14646-52. [CrossRef]

  • Hodge JW, Greiner JW, Tsang KY, Sabzevari H, Kudo-Saito C, Grosenbach DW, Gulley JL, Arlen PM, Marshall JL, Panicali D, Schlom J. Costimulatory molecules as adjuvants for immunotherapy. Front Biosci 2006; 11: 788-803. [PubMed] [CrossRef]

  • Chakraborty M, Abrams SI, Coleman CN, Camphausen K, Schlom J, Hodge JW. External beam radiation of tumors alters phenotype of tumor cells to render them susceptible to vaccine-mediated T-cell killing. Cancer Res 2004; 64(12): 4328-37. [CrossRef] [PubMed]

  • Gulley JL, Arlen PM, Bastian A, Morin S, Marte J, Beetham P, Tsang KY, Yokokawa J, Hodge JW, Menard C, Camphausen K, Coleman CN, Sullivan F, Steinberg SM, Schlom J, Dahut W. Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer. Clin Cancer Res 2005; 11(9): 3353-62. [CrossRef] [PubMed]

  • Miller AR, McBride WH, Hunt K, Economou JS. Cytokine-mediated gene therapy for cancer. Ann Surg Oncol 1994; 1(5): 436-50. [PubMed] [CrossRef]

  • Kemeny N, Childs B, Larchian W, Rosado K, Kelsen D. A phase II trial of recombinant tumor necrosis factor in patients with advanced colorectal carcinoma. Cancer 1990; 66(4): 659-63. [CrossRef] [PubMed]

  • Hallahan DE, Vokes EE, Rubin SJ, O'Brien S, Samuels B, Vijaykumar S, Kufe DW, Phillips R, Weichselbaum RR. Phase I dose-escalation study of tumor necrosis factor-alpha and concomitant radiation therapy. Cancer J Sci Am 1995; 1(3): 204-9. [PubMed]

  • Trinchieri G. Interleukin-12: a proinflammatory cytokine with immunoregulatory functions that bridge innate resistance and antigen-specific adaptive immunity. Annu Rev Immunol 1995; 13: 251-76. [CrossRef]

  • Trinchieri G. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol 2003; 3(2): 133-46. [CrossRef]

  • Voest EE, Kenyon BM, O'Reilly MS, Truitt G, D'Amato RJ, Folkman J. Inhibition of angiogenesis in vivo by interleukin 12. J Natl Cancer Inst 1995; 87(8): 581-6. [CrossRef]

  • Ogawa M, Yu WG, Umehara K, Iwasaki M, Wijesuriya R, Tsujimura T, Kubo T, Fujiwara H, Hamaoka T. Multiple roles of interferon-gamma in the mediation of interleukin 12-induced tumor regression. Cancer Res 1998; 58(11): 2426-32.

  • Brunda MJ, Luistro L, Warrier RR, Wright RB, Hubbard BR, Murphy M, Wolf SF, Gately MK. Antitumor and antimetastatic activity of interleukin 12 against murine tumors. J Exp Med 1993; 178(4): 1223-30. [CrossRef]

  • Seetharam S, Staba MJ, Schumm LP, Schreiber K, Schreiber H, Kufe DW, Weichselbaum RR. Enhanced eradication of local and distant tumors by genetically produced interleukin-12 and radiation. Int J Oncol 1999; 15(4): 769-73. [PubMed]

  • Lohr F, Hu K, Haroon Z, Samulski TV, Huang Q, Beaty J, Dewhirst MW, Li CY. Combination treatment of murine tumors by adenovirus-mediated local B7/IL12 immunotherapy and radiotherapy. Mol Ther 2000; 2(3): 195-203. [CrossRef]

  • Xian J, Yang H, Lin Y, Liu S. Combination nonviral murine interleukin 2 and interleukin 12 gene therapy and radiotherapy for head and neck squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 2005; 131(12): 1079-85. [CrossRef]

  • Fujita T, Timme TL, Tabata K, Naruishi K, Kusaka N, Watanabe M, Abdelfattah E, Zhu JX, Ren C, Ren C, Yang G, Goltsov A, Wang H, Vlachaki MT, Teh BS, Butler EB, Thompson TC. Cooperative effects of adenoviral vector-mediated interleukin 12 gene therapy with radiotherapy in a preclinical model of metastatic prostate cancer. Gene Ther 2007; 14(3): 227-36. [CrossRef]

  • Yang Y, Liu SZ, Fu SB. Anti-tumor effects of pNEgr-mIL-12 recombinant plasmid induced by X-irradiation and its mechanisms. Biomed Environ Sci 2004; 17(2): 135-43.

  • van HR, ten Hagen TL, Eggermont AM. TNF-alpha in cancer treatment: molecular insights, antitumor effects, and clinical utility. Oncologist 2006; 11(4): 397-408.

  • Sersa G, Willingham V, Milas L. Anti-tumor effects of tumor necrosis factor alone or combined with radiotherapy. Int J Cancer 1988; 42(1): 129-34. [PubMed] [CrossRef]

  • U. S. National Institutes of Health (Internet). Retrieved March 2008, from: http://ClinicalTrials.gov

  • Mauceri HJ, Hanna NN, Wayne JD, Hallahan DE, Hellman S, Weichselbaum RR. Tumor necrosis factor alpha (TNF-alpha) gene therapy targeted by ionizing radiation selectively damages tumor vasculature. Cancer Res 1996; 56(19): 4311-4. [PubMed]

  • Brem S, Brem H, Folkman J, Finkelstein D, Patz A. Prolonged tumor dormancy by prevention of neovascularization in the vitreous. Cancer Res 1976; 36(8): 2807-12. [PubMed]

  • Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100(1): 57-70. [PubMed] [CrossRef]

  • Denekamp J. Review article: angiogenesis, neovascular proliferation and vascular pathophysiology as targets for cancer therapy. Br J Radiol 1993; 66(783): 181-96. [CrossRef] [PubMed]

  • Folkman J, Hanahan D. Switch to the angiogenic phenotype during tumorigenesis. Princess Takamatsu Symp 1991; 22: 339-47. [PubMed]

  • Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 1996; 86(3): 353-64. [CrossRef] [PubMed]

  • Bergers G, Benjamin LE. Tumorigenesis and the angiogenic switch. Nat Rev Cancer 2003; 3(6): 401-10. [CrossRef] [PubMed]

  • Boehm T, Folkman J, Browder T, O'Reilly MS. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 1997; 390(6658): 404-7. [CrossRef] [PubMed]

  • Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995; 1(1): 27-31. [CrossRef] [PubMed]

  • Wachsberger P, Burd R, Dicker AP. Tumor response to ionizing radiation combined with antiangiogenesis or vascular targeting agents: exploring mechanisms of interaction. Clin Cancer Res 2003; 9(6): 1957-71. [PubMed]

  • Scappaticci FA. Mechanisms and future directions for angiogenesis-based cancer therapies. J Clin Oncol 2002; 20(18): 3906-27. [CrossRef] [PubMed]

  • Siemann DW, Warrington KH, Horsman MR. Targeting tumor blood vessels: an adjuvant strategy for radiation therapy. Radiother Oncol 2000; 57(1): 5-12. [PubMed] [CrossRef]

  • Siemann DW, Bibby MC, Dark GG, Dicker AP, Eskens FA, Horsman MR, Marme D, Lorusso PM. Differentiation and definition of vascular-targeted therapies. Clin Cancer Res 2005; 11(2): 416-20. [PubMed]

  • Kong HL, Crystal RG. Gene therapy strategies for tumor antiangiogenesis. J Natl Cancer Inst 1998; 90(4): 273-86. [CrossRef] [PubMed]

  • O'Reilly MS. Angiostatin: an endogenous inhibitor of angiogenesis and of tumor growth. EXS 1997; 79: 273-94.

  • Folkman J. Antiangiogenic gene therapy. Proc Natl Acad Sci U S A 1998; 95(16): 9064-6. [CrossRef]

  • Tandle A, Blazer DG, III, Libutti SK. Antiangiogenic gene therapy of cancer: recent developments. J Transl Med 2004; 2(1): 22. [PubMed] [CrossRef]

  • O'Reilly MS. Radiation combined with antiangiogenic and antivascular agents. Semin Radiat Oncol 2006; 16(1): 45-50.

  • Jain RK. Normalizing tumor vasculature with anti-angiogenic therapy: a new paradigm for combination therapy. Nat Med 2001; 7(9): 987-9. [PubMed] [CrossRef]

  • Siemann DW, Chaplin DJ, Horsman MR. Vascular-targeting therapies for treatment of malignant disease. Cancer 2004; 100(12): 2491-9. [CrossRef] [PubMed]

  • Wahl ML, Moser TL, Pizzo SV. Angiostatin and anti-angiogenic therapy in human disease. Recent Prog Horm Res 2004; 59(73-104. [CrossRef] [PubMed]

  • Folkman J. Antiangiogenesis in cancer therapy-endostatin and its mechanisms of action. Exp Cell Res 2006; 312(5): 594-607. [PubMed] [CrossRef]

  • Shi W, Teschendorf C, Muzyczka N, Siemann DW. Gene therapy delivery of endostatin enhances the treatment efficacy of radiation. Radiother Oncol 2003; 66(1): 1-9. [PubMed] [CrossRef]

  • Zheng AQ, Song XR, Yu JM, Wei L, Wang XW. Liposome transfected to plasmid-encoding endostatin gene combined with radiotherapy inhibits liver cancer growth in nude mice. World J Gastroenterol 2005; 11(28): 4439-42. [PubMed]

  • Luo X, Slater JM, Gridley DS. Enhancement of radiation effects by pXLG-mEndo in a lung carcinoma model. Int J Radiat Oncol Biol Phys 2005; 63(2): 553-64. [CrossRef]

  • Griscelli F, Li H, Cheong C, Opolon P, naceur-Griscelli A, Vassal G, Soria J, Soria C, Lu H, Perricaudet M, Yeh P. Combined effects of radiotherapy and angiostatin gene therapy in glioma tumor model. Proc Natl Acad Sci U S A 2000; 97(12): 6698-703. [CrossRef]

  • ten Hagen TL, Eggermont AM. Solid tumor therapy: manipulation of the vasculature with TNF. Technol Cancer Res Treat 2003; 2(3): 195-203.

  • Menon C, Ghartey A, Canter R, Feldman M, Fraker DL. Tumor necrosis factor-alpha damages tumor blood vessel integrity by targeting VE-cadherin. Ann Surg 2006; 244(5): 781-91. [PubMed] [CrossRef]

  • Weichselbaum RR, Kufe DW, Advani SJ, Roizman B. Molecular targeting of gene therapy and radiotherapy. Acta Oncol 2001; 40(6): 735-8. [PubMed] [CrossRef]

  • Robson T, Hirst DG. Transcriptional Targeting in Cancer Gene Therapy. J Biomed Biotechnol 2003; 2003(2): 110-37. [CrossRef]

  • Dachs GU, Dougherty GJ, Stratford IJ, Chaplin DJ. Targeting gene therapy to cancer: a review. Oncol Res 1997; 9(6-7): 313-25. [PubMed]

  • Goverdhana S, Puntel M, Xiong W, Zirger JM, Barcia C, Curtin JF, Soffer EB, Mondkar S, King GD, Hu J, Sciascia SA, Candolfi M, Greengold DS, Lowenstein PR, Castro MG. Regulatable gene expression systems for gene therapy applications: Progress and future challenges. Molecular Therapy 2005; 12(2): 189-211. [CrossRef]

  • Haviv YS, Curiel DT. Conditional gene targeting for cancer gene therapy. Adv Drug Deliv Rev 2001; 53(2): 135-54. [CrossRef] [PubMed]

  • Huang Q, Hu JK, Lohr F, Zhang L, Braun R, Lanzen J, Little JB, Dewhirst MW, Li CY. Heat-induced gene expression as a novel targeted cancer gene therapy strategy. Cancer Res 2000; 60(13): 3435-9. [PubMed]

  • Rubenstrunk A, Trollet C, Orsini C, Scherman D. Positive in vivo heterologous gene regulation by electric pulses delivery with metallothionein I gene promoter. J Gene Med 2005; 7(12): 1565-72. [CrossRef] [PubMed]

  • Chastel C, Jiricny J, Jaussi R. Activation of stress-responsive promoters by ionizing radiation for deployment in targeted gene therapy. DNA Repair (Amst) 2004; 3(3): 201-15. [CrossRef] [PubMed]

  • Nuyts S, Van ML, Barbe S, Lammertyn E, Theys J, Landuyt W, Bosmans E, Lambin P, Anne J. Insertion or deletion of the Cheo box modifies radiation inducibility of Clostridium promoters. Appl Environ Microbiol 2001; 67(10): 4464-70. [CrossRef] [PubMed]

  • Datta R, Taneja N, Sukhatme VP, Qureshi SA, Weichselbaum R, Kufe DW. Reactive oxygen intermediates target CC(A/T)6GG sequences to mediate activation of the early growth response 1 transcription factor gene by ionizing radiation. Proc Natl Acad Sci U S A 1993; 90(6): 2419-22. [CrossRef]

  • Marples B, Greco O, Joiner MC, Scott SD. Radiogenetic therapy: strategies to overcome tumor resistance. Curr Pharm Des 2003; 9(26): 2105-12. [CrossRef] [PubMed]

  • Joki T, Nakamura M, Ohno T. Activation of the radiosensitive EGR-1 promoter induces expression of the herpes simplex virus thymidine kinase gene and sensitivity of human glioma cells to ganciclovir. Hum Gene Ther 1995; 6(12): 1507-13. [PubMed]

  • Takahashi T, Namiki Y, Ohno T. Induction of the suicide HSV-TK gene by activation of the Egr-1 promoter with radioisotopes. Hum Gene Ther 1997; 8(7): 827-33. [PubMed]

  • Wang WD, Chen ZT, Li DZ, Duan YZ, Cao ZH. [Experimental study on lung carcinoma-targeted suicide gene therapy induced by irradiation]. Zhonghua Jie He He Hu Xi Za Zhi 2003; 26(2): 84-7.

  • Wu CM, Li XY, Huang TH. Anti-tumor effect of pEgr-IFNgamma gene-radiotherapy in B16 melanoma-bearing mice. World J Gastroenterol 2004; 10(20): 3011-5.

  • Coulter JA, McCarthy HO, Worthington J, Robson T, Scott S, Hirst DG. The radiation-inducible pE9 promoter driving inducible nitric oxide synthase radiosensitizes hypoxic tumour cells to radiation. Gene Ther 2008; 15(7): 495-503. [CrossRef]

  • Jin GH, Jin SZ, Liu Y, Xu RM, Yang JZ, Pan XN, Liu SZ. Therapeutic effect of gene-therapy in combination with local X-irradiation in a mouse malignant melanoma model. Biochem Biophys Res Commun 2005; 330(3): 975-81. [CrossRef]

  • Scott SD, Joiner MC, Marples B. Optimizing radiation-responsive gene promoters for radiogenetic cancer therapy. Gene Ther 2002; 9(20): 1396-402. [PubMed] [CrossRef]

  • Harada K, Ogden GR. An overview of the cell cycle arrest protein, p21(WAF1). Oral Oncol 2000; 36(1): 3-7. [CrossRef]

  • El-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B. WAF1, a potential mediator of p53 tumor suppression. Cell 1993; 75(4): 817-25.

  • Worthington J, Robson T, Murray M, O'Rourke M, Keilty G, Hirst DG. Modification of vascular tone using iNOS under the control of a radiation-inducible promoter. Gene Ther 2000; 7(13): 1126-31. [CrossRef] [PubMed]

  • McCarthy HO, Worthington J, Barrett E, Cosimo E, Boyd M, Mairs RJ, Ward C, McKeown SR, Hirst DG, Robson T. p21((WAF1))-mediated transcriptional targeting of inducible nitric oxide synthase gene therapy sensitizes tumours to fractionated radiotherapy. Gene Ther 2007; 14(3): 246-55. [CrossRef]

  • Espinosa JM, Emerson BM. Transcriptional regulation by p53 through intrinsic DNA/chromatin binding and site-directed cofactor recruitment. Mol Cell 2001; 8(1): 57-69. [CrossRef]

  • Nenoi M, Daino K, Ichimura S, Takahash S, Akuta T. Low-dose radiation response of the p21WAF1/CIP1 gene promoter transduced by adeno-associated virus vector. Exp Mol Med 2006; 38(5): 553-64. [CrossRef]

  • Vaupel P, Mayer A. Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev 2007; 26(2): 225-39. [CrossRef] [PubMed]

  • Brown JM, Wilson WR. Exploiting tumour hypoxia in cancer treatment. Nat Rev Cancer 2004; 4(6): 437-47. [CrossRef] [PubMed]

  • Brown JM. Tumor hypoxia in cancer therapy. Methods Enzymol 2007; 435(297-321. [PubMed]

  • Kizaka-Kondoh S, Inoue M, Harada H, Hiraoka M. Tumor hypoxia: a target for selective cancer therapy. Cancer Sci 2003; 94(12): 1021-8. [CrossRef]

  • Dachs GU, Stratford IJ. The molecular response of mammalian cells to hypoxia and the potential for exploitation in cancer therapy. Br J Cancer Suppl 1996; 27: 126-132.

  • Greco O, Patterson AV, Dachs GU. Can gene therapy overcome the problem of hypoxia in radiotherapy? J Radiat Res (Tokyo) 2000; 41(3): 201-12. [CrossRef] [PubMed]

  • Ruan H, Deen DF. Use of hypoxia-regulated gene expression in tumor-specific gene therapy. Curr Opin Investig Drugs 2001; 2(6): 839-43. [PubMed]

  • Greco O, Marples B, Joiner MC, Scott SD. How to overcome (and exploit) tumor hypoxia for targeted gene therapy. J Cell Physiol 2003; 197(3): 312-25. [CrossRef] [PubMed]

  • Shibata T, Giaccia AJ, Brown JM. Development of a hypoxia-responsive vector for tumor-specific gene therapy. Gene Ther 2000; 7(6): 493-8. [PubMed] [CrossRef]

  • Patterson AV, Williams KJ, Cowen RL, Jaffar M, Telfer BA, Saunders M, Airley R, Honess D, van der Kogel AJ, Wolf CR, Stratford IJ. Oxygen-sensitive enzyme-prodrug gene therapy for the eradication of radiation-resistant solid tumours. Gene Ther 2002; 9(14): 946-54. [CrossRef]

  • Scott SD, Greco O. Radiation and hypoxia inducible gene therapy systems. Cancer Metastasis Rev 2004; 23(3-4): 269-76. [PubMed] [CrossRef]

  • Greco O, Joiner MC, Doleh A, Powell AD, Hillman GG, Scott SD. Hypoxia- and radiation-activated Cre/loxP ‘molecular switch’ vectors for gene therapy of cancer. Gene Ther 2006; 13(3): 206-15. [PubMed] [CrossRef]

  • Teh BS, guilar-Cordova E, Vlachaki MT, Aguilar L, Mai WY, Caillouet J, Davis M, Miles B, Kadmon D, Ayala G, Lu HH, Chiu JK, Carpenter LS, Woo SY, Grant WH, III, Wheeler T, Thompson TC, Butler EB. Combining radiotherapy with gene therapy (from the bench to the bedside): a novel treatment strategy for prostate cancer. Oncologist 2002; 7(5): 458-66. [PubMed] [CrossRef]

  • Gossen M, Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci U S A 1992; 89(12): 5547-51. [CrossRef]

Comments (0)

Please log in or register to comment.