A cytochrome P450 2B6 meditated gene therapy strategy to enhance the effects of radiation or cyclophosphamide when combined with the bioreductive drug AQ4N

Journal of Gene Medicine

Volumn 7, Issue 7, 2005, Pages 851-859

  McErlane, Verna ^a   Yakkundi, Anita ^a   McCarthy, Helen O ^a   Hughes, Ciara M ^a   Patterson, Laurence H ^b   Hirst, David G ^a   Robson, Tracy ^a   McKeown, Stephanie R ^a  

^a UNIVERSITY OF ULSTER   (United Kingdom)

^b UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

AQ4N; Bioreductive; Cyclophosphamide; CYP2B6; GDEPT; Radiation

Indexed keywords

1,4 BIS[[2 (DIMETHYLAMINO N OXIDE)ETHYL]AMINO] 5,8 DIHYDROXYANTHRAQUINONE; COMPLEMENTARY DNA; CYCLOPHOSPHAMIDE; CYTOCHROME P450 2B6; CYTOCHROME REDUCTASE; CYTOTOXIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CANCER INHIBITION; CONTROLLED STUDY; DRUG EFFICACY; DRUG METABOLISM; FIBROSARCOMA; GENE DIRECTED ENZYME PRODRUG THERAPY; GENE THERAPY; GENETIC TRANSFECTION; HYPOXIC CELL; MULTIMODALITY CANCER THERAPY; NONHUMAN; PRIORITY JOURNAL; SOLID TUMOR; TRANSGENE; X RAY;

ANIMALS; ANTHRAQUINONES; ARYL HYDROCARBON HYDROXYLASES; CELL HYPOXIA; COMBINED MODALITY THERAPY; CYCLOPHOSPHAMIDE; DNA DAMAGE; DNA, NEOPLASM; FIBROSARCOMA; GENE THERAPY; HUMANS; MICE; MICE, INBRED C3H; NADPH-FERRIHEMOPROTEIN REDUCTASE; OXIDOREDUCTASES, N-DEMETHYLATING; PRODRUGS; RADIOTHERAPY; RECOMBINANT PROTEINS; TRANSFECTION; TRANSGENES; TUMOR CELLS, CULTURED;

EID: 20444413993     PISSN: 1099498X     EISSN: None     Source Type: Journal    
DOI: 10.1002/jgm.728     Document Type: Article

References (25)

1. Patterson LH, McKeown Sr. AQ4N: a new approach to hypoxia-activated cancer chemotherapy. Br J Cancer 2000; 83: 1589-1593.
2. Patterson LH, McKeown SR, Robson T, Gallagher R, Raleigh S, Orr S. Antitumour prodrug development using cytochrome P450 mediated activation. Anticancer Drug Design 1999; 14: 473-486.
3. McKeown SR, Hejmadi MV, McIntyre IA, Patterson LH. AQ4N: an alkylamioanthraquinone N-oxide showing bioreductive potential and positive interaction with radiation in vivo. Br J Cancer 1995; 72: 76-81.
4. Hejmadi MV, McKeown SR, Friery OP, McIntyre IA, Patterson LH, Hirst DG. DNA damage following combination of radiation with the bioreductive drug AQ4N: possible selective toxicity to oxic and hypoxic tumour cells. Br J Cancer 1996; 73: 499-505.
5. Friery OP, Gallagher R, Murray MM, et al. Enhancement of the anti-tumour effect of cyclophosphamide by the bioreductive drugs AQ4N and tirapazamine. Br J Cancer 2000; 82: 1469-1473.
6. Gallagher R, Hughes CM, Murray MM, et al. The chemopotentiation of cisplatin by the novel bioreductive drug AQ4N. Br J Cancer 2001; 85: 625-629.
7. Greco O, Dachs GU. Gene directed enzyme/prodrug therapy of cancer: historical appraisal and future prospectives. J Cell Physiol 2001; 187: 22-36.
8. McKeown SR, Ward C, Robson T. Gene directed enzyme prodrug therapy (GDEPT) - a current assessment. Curr Opin Mol Ther 2004; 6: 421-435.
9. Chen L, Yu LJ, Waxman DJ. Potentiation of cytochrome P450/cyclophosphamide-based cancer gene therapy by coexpression of the P450 reductase gene. Cancer Res 1997; 57: 4830-4837.
10. Jounaidi Y, Hecht JED, Waxman DJ. Retroviral transfer of human cytochrome P450 genes for oxazaphosphorine-based cancer gene therapy. Cancer Res 1998; 58: 4391-4401.
11. McCarthy HO, Yakkundi A, McErlane V, et al. Bioreductive GDEPT using cytochropme 3A4 in combination with AQ4N. Cancer Gene Ther 2003; 10: 40-48.
12. 2 predicts survival in advanced cancer of the uterine cervix. Radiother Oncol 1993; 26: 45-50.
13. Brown JM, Giaccia AJ. The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res 1998; 58: 1408-1416.
14. Touraine RL, Vahanian N, Ramsey WJ, Blaese RM. Enhancement of the herpes simplex virus thymidine kinase ganciclovir bystander effect and its anti-tumour efficacy in vivo by pharmacologic manipulation of gap junctions. Human Gene Ther 1998; 9: 2385-2391.
15. Smith PJ, Desnoyers R, Blunt N, Giles Y, Patterson LH, Watson JV. Flow cytometric analysis and confocal imaging of anticancer alkylaminoanthraquinones and their N-oxides in intact human cells using 647-nm krypton laser excitation. Cytometry 1997; 27: 43-53.
16. Twentyman PR, Brown JM, Gray JW, Franko AJ, Scoles MA, Kallman RF. A new mouse tumour model system (RIF-1) for comparison of end-point studies. J Natl Cancer Inst 1980; 64: 595-604.
17. Chen L, Waxman DJ. Cytochrome P450 gene-directed enzyme prodrug therapy (GDEPT) for cancer. Curr Pharm Des 2002; 8: 1405-1416.
18. Jounaidi Y, Waxman DJ. Frequent, moderate-dose cyclophosphamide administration improves the efficacy of cytochrome P450/cyctochrome P450 reductase-based cancer gene therapy. Cancer Res 2001; 61: 4437-4444.
19. Jounaidi Y, Waxman DJ. Use of replication-conditional adenovirus as a helper system to enhance delivery of P450 prodrug-activation genes for cancer therapy. Cancer Res 2004; 64: 292-303.
20. Jounaidi Y, Waxman DJ. Combination of the bioreductive drug tirapazamine with the chemotherapeutic prodrug cyclophosphamide for P450/P450-reductase-based cancer gene therapy. Cancer Res 2000; 60: 3761-3769.
21. Raleigh SM, Wanogho E, Burke MD, McKeown SR, Patterson LH. Involvement of human cytochromes P450 (CYP) in the reductive metabolism of AQ4N, a hypoxia activated anthraquinone di-N-oxide prodrug. Int J Radiat Oncol Biol Phys 1998; 42: 763-767.
22. Raleigh SM, Tien P, Patterson LH. Involvement of haem and cytochrome P450 reductase in the bioreduction of the anthraquinone di-N-oxide AQ4N. Proc Am Asn Cancer Res 1995; 36: Abstract 3584.
23. Patterson LH. Rationale for the use of aliphatic amine N-oxides of cytotoxic anthraquinones as prodrug DNA binding agents: a new class of bioreductive agent. Cancer Metastasis Rev 1993; 12: 119-134.
24. Benghiat A, Steward WP, Loadman PM, et al. Phase 1 dose escalation study of AQ4N, a selective hypoxic cell cytotoxin, with fractionated radiotherapy (RT) - first report. Proc Am Assoc Clin Oncol 2004; Abstract 2091.
25. Kan O, Griffiths L, Baban D, et al. Direct retroviral delivery of human cytochrome P450 2B6 for gene-directed enzyme prodrug therapy of cancer. Cancer Gene Ther 2001; 8: 473-482.