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.

  • Original Article
  • Published:

Cancer gene therapy: an awkward adolescence

Cancer Gene Therapy volume 10, pages 501–508 (2003)Cite this article

Abstract

At the Eleventh International Conference on Gene Therapy of Cancer (December 12–14, 2002, San Diego, CA) progress on using gene transfer technology to treat cancer was presented. Although there is as yet no cancer gene therapy being marketed, considerable progress has been made in defining likely strategies and likely targets for gene therapy of cancer. These strategies, including viral and non-viral delivery systems, and potential targets in cancer cells linked to our developing knowledge of cancer cell biology, are reviewed in this paper. Use of gene therapy to sensitize tumors to radiation and chemotherapy is one promising area of investigation. Some of the ancillary benefits of research on cancer gene therapy, including the development of public-private partnerships, recruitment of laboratory scientists into clinical research, and credentialing of potential cancer cell targets for therapies other than gene therapy, are noted.

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

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Aebersold P, Kasid A, Rosenberg SA . Selection of gene-marked tumor infiltrating lymphocytes from post-treatment biopsies: a case study. Hum Gene Ther. 1990;1:373–384.

    Article  CAS  Google Scholar 

  2. Cai Q, Rubin JT, Lotze MT . Genetically marking human cells — results of the first clinical gene transfer studies. Cancer Gene Ther. 1995;2:125–136.

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  5. Horio Y, Hasegawa Y, Sekido Y, Takahasi M, Roth JA, Shimokata K . Synergistic effects of adenovirus expressing wild-type p53 on chemosensitivity of non small cell lung cancer cells. Cancer Gene Ther. 2000;7:537–544.

    Article  CAS  Google Scholar 

  6. Nemunaitis J . Live viruses in cancer treatment. Oncology. 2002;16:1483–1492.

    PubMed  Google Scholar 

  7. Demers GW, Harris MP, Wen SF, Engler H, Nielsen LL, Maneval DC . A recombinant adenoviral vector expressing full-length human retinoblastoma susceptibility gene inhibits human tumor cell growth. Cancer Gene Ther. 1998;5:207–214.

    CAS  PubMed  Google Scholar 

  8. Sauane M, Gopalkrishnan RV, Sarkar D, et al. MDA-7/IL-24: novel cancer growth suppressing and apoptosis inducing cytokine. Cytokine Growth Factor Rev. 2003;14:35–51.

    Article  CAS  Google Scholar 

  9. Caudell EG, Mumm JB, Poindexter N, et al. The protein product of the tumor suppressor gene, melanoma differentiation-associated gene 7, exhibits immunostimulatory activity and is designated IL-24. J Immunol. 2002;168:6041–6046.

    Article  CAS  Google Scholar 

  10. Ji L, Nishizaki M, Gao B, et al. Expression of several genes in the human chromosome 3p21.3 homozygous deletion region by an adenovirus vector results in tumor suppressor activities in vitro and in vivo. Cancer Res. 2002;62:2715–2720.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Heinicke T, Radziwill G, Nawrath M, Rommel C, Pavlovic J, Moelling K . Retroviral gene transfer of dominant negative raf-1 mutants suppresses Ha-ras-induced transformation and delays tumor formation. Cancer Gene Ther. 2000;7:697–706.

    Article  CAS  Google Scholar 

  12. Lee CT, Park KH, Adachi Y, et al. Recombinant adenoviruses expressing dominant negative insulin-like growth factor-I receptor demonstrate antitumor effects on lung cancer. Cancer Gene Ther. 2003;10:57–63.

    Article  CAS  Google Scholar 

  13. Benovich M, Olive M, Reed E, O'Connell B, Vinson C . Adenoviral delivery of A-FOS, an AP-1 dominant negative, selectively inhibits drug resistance in two human cancer cell lines. Cancer Gene Ther. 2002;9:62–70.

    Article  Google Scholar 

  14. Reed JC . Apoptosis-based therapies. Nat Rev Drug Discov. 2002;1:111–121.

    Article  CAS  Google Scholar 

  15. Roth W, Reed JC . Apoptosis and cancer: When BAX is TRAILing away. Nat Med. 2002;8:216–218.

    Article  CAS  Google Scholar 

  16. Heise CC, Williams A, Olesch J, Kirn DH . Efficacy of a replication-competent adenovirus (ONYX-015) following intratumoral injection: intratumoral spread and distribution effects. Cancer Gene Ther. 1999;6:499–504.

    Article  CAS  Google Scholar 

  17. Biederer C, Ries S, Brandts CH, McCormick F . Replication-selective viruses for cancer therapy. J Mol Med. 2002;80:163–175.

    Article  CAS  Google Scholar 

  18. Yoon TK, Shichinohe T, Laquerre S, Kasahara N . Selectively replicating adenoviruses for oncolytic therapy. Curr Cancer Drug Targets. 2001;1:85–107.

    Article  CAS  Google Scholar 

  19. Pecora AL, Rizvi N, Cohen Gi, et al. Phase I trial of intravenous administration of PV701, an oncolytic virus, in patients with advanced solid cancers. J Clin Oncol. 2002;20:2251–2266.

    Article  CAS  Google Scholar 

  20. Soifer H, Higo C, Logg CR, et al. A novel, helper-dependent, adenovirus–retrovirus hybrid vector: stable transduction by a two-stage mechanism. Mol Ther. 2002;5:599–608.

    Article  CAS  Google Scholar 

  21. Moolten FL . Drug sensitivity (“suicide”) genes for selective cancer chemotherapy. Cancer Gene Ther. 1994;1:279–287.

    CAS  PubMed  Google Scholar 

  22. Yoshida Y, Tomizawa M, Bahar R, et al. A promoter region of midkine gene can activate transcription of an exogenous suicide gene in human pancreatic cancer. Anticancer Res. 2002;22:117–120.

    CAS  PubMed  Google Scholar 

  23. Wesseling JG, Yamamoto M, Adachi Y, et al. Midkine and cyclooxygenase-2 promoters are promising for adenoviral vector gene delivery of pancreatic carcinoma. Cancer Gene Ther. 2001;8:990–996.

    Article  CAS  Google Scholar 

  24. DeWeese TL, van der Poel H, Li S, et al. A phase I trial of CV706, a replication-competent, PSA selective oncolytic adenovirus, for the treatment of locally recurrent prostate cancer following radiation. Cancer Res. 2001;61:7464–7472.

    CAS  PubMed  Google Scholar 

  25. Marintiello-Wilks R, Tsatralis T, Russell P, et al. Transcription-targeted gene therapy for androgen-independent prostate cancer. Cancer Gene Ther. 2002;9:443–452.

    Article  Google Scholar 

  26. Rasmussen H, Rasmussen C, Lempicki M, et al. 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;9:951–957.

    Article  CAS  Google Scholar 

  27. Gottesman MM, Fojo T, Bates SE . Multidrug resistance in cancer: role of ATP-dependent transporters. Nat Rev Cancer. 2002;2:48–58.

    Article  CAS  Google Scholar 

  28. Braun SE, McIvor RS, Davidson AS, et al. Retrovirally mediated gene transfer of Arg22 and Tyr22 forms of dihydrofolate reductase into the hematopoietic cell line K562: a comparison of methotrexate resistance. Cancer Gene Ther. 1997;4:26–32.

    CAS  PubMed  Google Scholar 

  29. Cowan KH, Moscow JA, Huang H, et al. Paclitaxel chemotherapy after autologous stem-cell transplantation and engraftment of hematopoietic cells transduced with a retrovirus containing the multidrug resistance complementary DNA (MDR1) in metastatic breast cancer patients. Clin Cancer Res. 1999;5:1619–1628.

    CAS  PubMed  Google Scholar 

  30. Dalal RM, Lotze MT . Immunotherapy of metastasis. Surg Oncol Clin N Am. 2001;10:433–447.

    Article  Google Scholar 

  31. Reyes-Sandoval A, Ertl HC . DNA vaccines. Curr Mol Med. 2001;1:217–243.

    Article  CAS  Google Scholar 

  32. Wang L, Qi X, Sun Y, Liang L, Ju D . Adenovirus-mediated combined P16 gene and GM-CSF gene therapy for the treatment of established tumor and induction of antitumor immunity. Cancer Gene Ther. 2002;9:819–824.

    Article  CAS  Google Scholar 

  33. Bauerschmitz GJ, Barker SD, Hemminki A . Adenoviral gene therapy for cancer: from vectors to targeted and replication competent agents (Review). Int J Oncol. 2002;21:1161–1174.

    CAS  PubMed  Google Scholar 

  34. Haviv YS, Blackwell JL, Kanerva A, et al. Adenoviral gene therapy for renal cancer requires retargeting to alternative cellular receptors. Cancer Res. 2002;62:4273–4281.

    CAS  PubMed  Google Scholar 

  35. Raper SE, Yudkoff M, Chirmule N, et al. A pilot study of in vivo liver-directed gene transfer with an adenoviral vector in partial ornithine transcarbamylase deficiency. Hum Gene Ther. 2002;13:163–175.

    Article  CAS  Google Scholar 

  36. Marshall E . Gene therapy death prompts review of adenovirus vector. Science. 1999;286:2244–2245.

    Article  CAS  Google Scholar 

  37. Anderson WF (ed.). NIH report: assessment of adenoviral vector safety and toxicity: report of the National Institutes of Health Recombinant DNA Advisory Committee. Cancer Gene Ther. 2002;13:3–13.

  38. Shichinohe T, Bochner BH, Mizutani K, et al. Development of lentiviral vectors for antiangiogenic gene delivery. Cancer Gene Ther. 2001;8:879–889.

    Article  CAS  Google Scholar 

  39. Kafri T, van Praag H, Ouyang L, Gage FH, Verma IM . A packaging cell line for lentivirus vectors. J Virol. 1999;73:576–584.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Fischer A, Hacein-Bey S, Cavazzana-Calvo M . Gene therapy of severe combined immunodeficiencies. Nat Rev Immunol. 2002;2:615–621.

    Article  CAS  Google Scholar 

  41. Hacein-Bey-Abina S, von Kalle C, Schmidt M, et al. A serious adverse event after successful gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2003;348:255–256.

    Article  Google Scholar 

  42. Barnett FH, Rainov NG, Ikeda K, et al. Selective delivery of herpes virus vectors to experimental brain tumors using RMP-7. Cancer Gene Ther. 1999;6:14–20.

    Article  CAS  Google Scholar 

  43. Lilley CE, Branston RH, Coffin RS . Herpes simplex virus vectors for the nervous system. Curr Gene Ther. 2001;1:339–358.

    Article  CAS  Google Scholar 

  44. Kimchi-Sarfaty C, Ben-Nun-Shaul O, Rund D, Oppenheim A, Gottesman MM . In vitro-packaged SV40 pseudovirions as highly efficient vectors for gene transfer. Hum Gene Ther. 2002;13:299–310.

    Article  CAS  Google Scholar 

  45. Paul S, Regulier E, Rooke R, et al. Tumor gene therapy by MVA-mediated expression of T-cell-stimulating antibodies. Cancer Gene Ther. 2002;9:470–477.

    Article  CAS  Google Scholar 

  46. Odin L, Favrot M, Poujol D, et al. Canarypox virus expressing wild type p53 for gene therapy in murine tumors mutated in p53. Cancer Gene Ther. 2001;8:87–98.

    Article  CAS  Google Scholar 

  47. Templeton NS, Lasic DD, Frederik PM, Strey HH, Roberts DD, Pavlakis GN . Improved DNA : liposome complexes for increased systemic delivery and gene expression. Nat Biotechnol. 1997;15:647–652.

    Article  CAS  Google Scholar 

  48. Orson FM, Kinsey BM, Bhogal BS, Song L, Densmore CL, Barry MA . Targeted delivery of expression plasmids to the lung via macroaggregated polyethylenimine–albumin conjugates. Methods Mol Med. 2003;75:575–590.

    CAS  PubMed  Google Scholar 

  49. Cunningham C, Nemunaitis J . A phase I trial of genetically modified Salmonella typhimurium expressing cytosine deaminase (TAPET-CD, VNP20029) administered by intratumoral injection in combination with 5-fluorocytosine for patients with advanced or metastatic cancer. Hum Gene Ther. 2001;10:1594–1596.

    Google Scholar 

  50. Devi GR . Prostate cancer; status of current treatments and emerging antisense-based therapies. Curr Opin Mol Ther. 2002;4:138–148.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

I am grateful to George Leiman for editorial assistance and to Amy Patterson for comments on the manuscript.

Author information

Authors and Affiliations

  1. Department of Health and Human Services, Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, 20892, Maryland, USA

    Michael M Gottesman

Authors
  1. Michael M Gottesman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael M Gottesman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gottesman, M. Cancer gene therapy: an awkward adolescence. Cancer Gene Ther 10, 501–508 (2003). https://doi.org/10.1038/sj.cgt.7700602

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.cgt.7700602

Keywords

This article is cited by

Search

Advanced search

Quick links