SpringerProtocols: Abstract: Selection of Cytochrome P450 Genes for Use in Prodrug Activation-Based Cancer Gene Therapy

Selection of Cytochrome P450 Genes for Use in Prodrug Activation-Based Cancer Gene Therapy

By: Jodi E. D. Hecht², David J. Waxman²

Abstract

Full Text

Download PDF (80K)

Prodrug activation-based cancer gene therapy is a molecular strategy to improve the efficacy of cancer chemotherapy by conferring upon tumor cells the capability to metabolize specific anticancer prodrugs into lethal intracellular toxins. The overall goal of this strategy is to increase the generation of cytotoxic drug metabolites locally, at their site of action within the tumor. This therapy can provide for an increase in drug efficacy and potentially also a reduction in host toxicity, which may be achieved by a lowering of the therapeutically effective drug dosage, thereby reducing the need to expose host tissues to high cytotoxic plasma drug concentrations. This chapter describes the cytochrome P450-based prodrug activation strategy for cancer gene therapy , with a particular emphasis on the selection of suitable P450 gene/prodrug combinations.

Affiliation(s): (2) Department of Biology, Boston University, Boston, MA

Book Title: Gene Therapy of Cancer: Methods and Protocols

Series: Methods in Molecular Medicine | Volume: 35 | Pub. Date: Feb-17-2000 | Page Range: 77-83 | DOI: 10.1385/1-59259-086-1:77

Subject: Cancer Research

References

Download References

1.	Wei, M. X., Tamiya, T., Chase, M., Boviatsis, E. J., Chang, T. K. H., Kowall, N. W., et al. (1994) Experimental tumor therapy in mice using the cyclophosphamideactivating cytochrome P450 2B1 gene. Hum. Gene Ther. 5, 969–978.

2.	Chen, L. and Waxman, D. J. (1995) Intratumoral activation and enhanced chemotherapeutic effect of oxazaphosphorines following cytochrome P450 gene transfer: development of a combined chemotherapy/cancer gene therapy strategy. Cancer Res. 55, 581–589.

3.	Waxman, D. J., Chen, L., Hecht, J. E. D., and Jounaidi, Y. (1998) Cytochrome P450-based cancer gene therapy: recent advances and future prospects. Drug Metab. Rev. 31, 503–522.

4.	Moolten, F. L. (1994) Drug sensitivity (&quote;suicide&quote;) genes for selective cancer chemotherapy. Cancer Gene Ther. 1, 279–287.

5.	Freeman, S. M., Whartenby, K. A., Freeman, J. L., Abboud, C. N., and Marrogi, A. J. (1996) In situ use of suicide genes for cancer therapy. Semin. Oncol. 23, 31–45.

6.	Roth, J. A. and Cristiano, R. J. (1997) Gene therapy for cancer: what have we done and where are we going? J. Natl. Cancer Inst. 89, 21–39.

7.	Pope, I. M., Poston, G. J., and Kinsella, A. R. (1997) The role of the bystander effect in suicide gene therapy. Eur. J. Cancer 33, 1005–1016.

8.	LeBlanc, G. A. and Waxman, D. J. (1989) Interaction of anticancer drugs with hepatic monooxygenase enzymes. Drug Metab. Rev. 20, 395–439.

9.	Kivisto, K. T., Kroemer, H. K., and Eichelbaum, M. (1995) The role of human cytochrome P450 enzymes in the metabolism of anticancer agents: implications for drug interactions. Br. J. Clin. Pharmacol. 40, 523–530.

10.	Smith, G., Harrison, D. J., East, N., Rae, F., Wolf, H., and Wolf, C. R. (1993) Regulation of cytochrome P450 gene expression in human colon and breast tumour xenografts. Br. J. Cancer 68, 57–63.

11.	Huang, Z., Fasco, M. J., Figge, H. L., Keyomarsi, K., and Kaminsky, L. S. (1996) Expression of cytochromes P450 in human breast tissue and tumors. Drug Metab. Dispos. 24, 899–905.

12.	Chang, T. K. H., Weber, G. F., Crespi, C. L., and Waxman, D. J. (1993) Differential activation of cyclophosphamide and ifosphamide by cytochromes P450 2B and 3A in human liver microsomes. Cancer Res. 53, 5629–5637.

13.	Walker, D., Flinois, J. P., Monkman, S. C., Beloc, C., Boddy, A. V., Cholerton, S., et al. (1994) Identification of the major human hepatic cytochrome P450 involved in activation and N-dechloroethylation of ifosfamide. Biochem. Pharmacol. 47, 1157–1163.

14.	Dehal, S. S. and Kupfer, D. (1997) CYP2D6 catalyzes tamoxifen 4-hydroxylation in human liver. Cancer Res. 57, 3402–3406.

15.	Rainov, N. G., Dobberstein, K. U., Sena-Esteves, M., Herrlinger, U., Kramm, C. M., Philpot, R. M., et al. (1998) New prodrug activation gene therapy for cancer using cytochrome P450 4B1 and 2-Aminoanthracene/4-Ipomeanol. Human Gene Ther. 9, 1261–1273.

16.	Chen, L., Yu, L. J., and Waxman, D. J. (1997) Potentiation of cytochrome P450/ cyclophosphamide-based cancer gene therapy by coexpression of the P450 reductase gene. Cancer Res. 57, 4830–4837.

17.	Chase, M., Chung, R. Y., and Chiocca, E. A. (1998) An oncolytic viral mutant that delivers the CYP2B1 transgene and augments cyclophosphamide chemotherapy. Nature Biotech. 16, 444–448.

18.	Chen, L., Waxman, D. J., Chen, D., and Kufe, D. W. (1996) Sensitization of human breast cancer cells to cyclophosphamide and ifosfamide by transfer of a liver cytochrome P450 gene. Cancer Res. 56, 1331–1340.

19.	Jounaidi, Y., Hecht, J. E. D., and Waxman, D. J. (1998) Retroviral transfer of cytochrome P450 genes for oxazaphosphorine-based cancer gene therapy. Cancer Res. 58, 4391–4401.

20.	Clarke, L. and Waxman, D. J. (1989) Oxidative metabolism of cyclophosphamide: identification of the hepatic monooxygenase catalysts of drug activation. Cancer Res. 49, 2344–2350.

21.	Chang, T. K., Yu, L., Goldstein, J. A., and Waxman, D. J. (1997) Identification of the polymorphically expressed CYP2C19 and the wild-type CYP2C9-ILE359 allele as low-Km catalysts of cyclophosphamide and ifosfamide activation. Pharmacogenetics 7, 211–221.

22.	Weber, G. F. and Waxman, D. J. (1993) Activation of the anti-cancer drug ifosphamide by rat liver microsomal P450 enzymes. Biochem. Pharmacol. 45, 1685–1694.

23.	Roy, P., Yu, L. J., Crespi, C. L., and Waxman, D. J. (1999) Development of a substrate-activity based approach to identify the major human liver P450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P450 profiles. Drug Metab. Rev. 27, 655–666.

24.	Nelson, D. R., Koymans, L., Kamataki, T., Stegeman, J. J., Feyereisen, R., Waxman, D. J., et al. (1996) Cytochrome P450 superfamily: Update on new sequences, gene mapping, accession numbers, and nomenclature. Pharmacogenetics 6, 1–42.

25.	Mesnil, M., Piccoli, C., Tiraby, G., Willecke, K., and Yamasaki, H. (1996) Bystander killing of cancer cells by herpes simplex virus thymidine kinase gene is mediated by connexins. Proc. Natl. Acad. Sci. USA 93, 1831–1835.

26.	Gagandeep, S., Brew, R., Green, B., Christmas, S. E., Klatzmann, D., Poston, G. J., and Kinsella, A. R. (1996) Prodrug-activated gene therapy: involvement of an immunological component in the &quote;bystander effect.&quote; Cancer Gene Ther. 3, 83–88.

27.	Aghi, M., Chou, T. C., Suling, K., Breakfield, X. O., and Chiocca, E. A. (1999) Multimodal cancer treatment mediated by a replicating oncolytic virus that delivers the oxazaphosphorine/rat cytochrome P450-2B1 and ganciclovir/herpes simplex virus thymidine kinase gene therapies. Cancer Res. 59, 3861–3865.

28.	Dachs, G. U., Dougherty, G. J., Stratford, I. J., and Chaplin, D. J. (1997) Targeting gene therapy to cancer: a review. Oncol. Res. 9, 313–325.

29.	Miller, N. and Whelan, J. (1997) Progress in transcriptionally targeted and regulatable vectors for genetic therapy. Hum. Gene Ther. 8, 803–815.

30.	Dachs, G. U., Patterson, A. V., Firth, J. D., Ratcliffe, P. J., Townsend, K. M., Stratford, I. J., and Harris, A. L. (1997) Targeting gene expression to hypoxic tumor cells. Nat. Med. 3, 515–520.

31.	Brown, J. M. and Giaccia, A. J. (1998) The unique physiology of solid tumors: opportunities (and problems) for cancer therapy. Cancer Res. 58, 1408–1416.

Comments (Loading...)

Post comment/View all comments