Adenovirus p 16 gene therapy for prostate cancer

James A. Allay, Mitchell S. Steiner, Yu Zhang, P. Christopher, Reed Jody Cockroft, Yi Lu

Research output: Contribution to journalArticle

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Abstract

Surgery, radiation, or hormone deprivation alone does not adequately affect local control of clinical or pathologic stage T3 prostate cancer. Lack of local cancer control ultimately leads to a higher incidence of morbidity, distant metastasis, and decreased survival, with patients having disease-specific mortality exceeding 75%. Other novel therapies against this devastating and common disease are needed for the achievement of longterm local cancer control. For this purpose, therapeutic interventions should target prostate-cancer cells at the molecular and cellular level in ways not possible by current modalities of cancer treatment. Any strategy that can modify the biologic behavior of these cells may potentially have the most significant clinical impact. As prostate cancer represents an accumulation of genetic mutations that causes a prostate cell to lose the ability to control its growth, one new approach against prostate cancer may be gene therapy. Identification of key missing or mutated tumor-suppressor genes that, when replaced, may inhibit or destroy prostate-cancer cells may have the best chance of clinical success. One such gene appears to be tumor-suppressor gene pi6 (also known as MTS1. INK4A, and CDKN2). Tumor-suppressor gene pi6 is an important negative cell-cycle regulator whose functional loss may significantly contribute to malignant transformation and progression. Alterations in the pi6 gene and its protein expression often occur in prostate cancer. An adenoviral vector containing wild-type pi6 (Adpl6) had a high transduction efficiency in prostate-cancer cells both in vitro and in vivo. Moreover, prostate tumors injected with Adpl6 expressed pi6 and the adenoviral vector expressed the transgene for up to 14 days. Wild-type pi6 inhibited prostate-cancer proliferation in vitro and markedly suppressed tumors in vivo. Pathologic evaluation of the Adpl6-treated tumors showed dose-dependent necrosis and fibrosis. Although the mechanism of pi6 inhibition in cancer remains to be elucidated, senescence and apoptosis may both be important; however, the data suggest that p 16induced growth inhibition can function independently of the retinoblastoma gene product.

Original languageEnglish (US)
Pages (from-to)111-120
Number of pages10
JournalWorld Journal of Urology
Volume18
Issue number2
DOIs
StatePublished - Jan 1 2000

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Adenoviridae
Genetic Therapy
Prostatic Neoplasms
Tumor Suppressor Genes
Neoplasms
Prostate
Retinoblastoma Genes
Aptitude
Growth
Transgenes
Cell Cycle
Fibrosis
Necrosis
Therapeutics
Hormones
Radiation
Apoptosis
Neoplasm Metastasis
Morbidity
Efficiency

All Science Journal Classification (ASJC) codes

  • Urology

Cite this

Allay, J. A., Steiner, M. S., Zhang, Y., Christopher, P., Cockroft, R. J., & Lu, Y. (2000). Adenovirus p 16 gene therapy for prostate cancer. World Journal of Urology, 18(2), 111-120. https://doi.org/10.1007/s003450050182

Adenovirus p 16 gene therapy for prostate cancer. / Allay, James A.; Steiner, Mitchell S.; Zhang, Yu; Christopher, P.; Cockroft, Reed Jody; Lu, Yi.

In: World Journal of Urology, Vol. 18, No. 2, 01.01.2000, p. 111-120.

Research output: Contribution to journalArticle

Allay, JA, Steiner, MS, Zhang, Y, Christopher, P, Cockroft, RJ & Lu, Y 2000, 'Adenovirus p 16 gene therapy for prostate cancer', World Journal of Urology, vol. 18, no. 2, pp. 111-120. https://doi.org/10.1007/s003450050182
Allay JA, Steiner MS, Zhang Y, Christopher P, Cockroft RJ, Lu Y. Adenovirus p 16 gene therapy for prostate cancer. World Journal of Urology. 2000 Jan 1;18(2):111-120. https://doi.org/10.1007/s003450050182
Allay, James A. ; Steiner, Mitchell S. ; Zhang, Yu ; Christopher, P. ; Cockroft, Reed Jody ; Lu, Yi. / Adenovirus p 16 gene therapy for prostate cancer. In: World Journal of Urology. 2000 ; Vol. 18, No. 2. pp. 111-120.
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