Estrogen enhances the efficacy of an oncolytic HSV-1 mutant in the treatment of estrogen receptor-positive breast cancer

  • Authors:
    • Brendon M. Stiles
    • Prasad S. Adusumilli
    • Stephen F. Stanziale
    • David P. Eisenberg
    • Amit Bhargava
    • Teresa H. Kim
    • Mei-Ki Chan
    • Rumana Huq
    • Mithat Gonen
    • Yuman Fong
  • View Affiliations

  • Published online on: June 1, 2006     https://doi.org/10.3892/ijo.28.6.1429
  • Pages: 1429-1439
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Abstract

Oncolytic herpes simplex virus-1 (HSV-1) mutants selectively replicate in and lyse tumor cells. Viral replication is dependent on the cellular proliferative mechanism. Estrogen increases cellular proliferation and decreases apoptosis in estrogen receptor-positive (ER+) human breast cancer cells. We hypothesize that the cellular changes produced by estrogen may enhance oncolytic viral replication and improve the treatment of ER+ breast cancer cells. Estrogen increased proliferation and replication of the HSV-1 mutant, NV1066, in ER+ breast cancer cells. Additionally, cells grown with estrogen had lower rates of apoptosis and higher bcl-2 levels at baseline and after infection. Estrogen enhanced the oncolytic effect of NV1066, with cell kills of 95% and 97% at MOIs of 0.1 and 0.5, compared to 53 and 87% respectively without estrogen (p<0.001). Therapy of ER+ human breast cancer cells with a replication-competent HSV-1 mutant is improved in the presence of estrogen, in contrast to more standard therapies, such as chemotherapy and radiation, which demonstrate decreased efficacy in similar conditions. These data provide the mechanistic basis for the use of oncolytic HSV-1 in patients with hormone receptor-positive breast cancer, particularly if the disease progresses with conventional therapies.

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June 2006
Volume 28 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Stiles BM, Adusumilli PS, Stanziale SF, Eisenberg DP, Bhargava A, Kim TH, Chan M, Huq R, Gonen M, Fong Y, Fong Y, et al: Estrogen enhances the efficacy of an oncolytic HSV-1 mutant in the treatment of estrogen receptor-positive breast cancer. Int J Oncol 28: 1429-1439, 2006.
APA
Stiles, B.M., Adusumilli, P.S., Stanziale, S.F., Eisenberg, D.P., Bhargava, A., Kim, T.H. ... Fong, Y. (2006). Estrogen enhances the efficacy of an oncolytic HSV-1 mutant in the treatment of estrogen receptor-positive breast cancer. International Journal of Oncology, 28, 1429-1439. https://doi.org/10.3892/ijo.28.6.1429
MLA
Stiles, B. M., Adusumilli, P. S., Stanziale, S. F., Eisenberg, D. P., Bhargava, A., Kim, T. H., Chan, M., Huq, R., Gonen, M., Fong, Y."Estrogen enhances the efficacy of an oncolytic HSV-1 mutant in the treatment of estrogen receptor-positive breast cancer". International Journal of Oncology 28.6 (2006): 1429-1439.
Chicago
Stiles, B. M., Adusumilli, P. S., Stanziale, S. F., Eisenberg, D. P., Bhargava, A., Kim, T. H., Chan, M., Huq, R., Gonen, M., Fong, Y."Estrogen enhances the efficacy of an oncolytic HSV-1 mutant in the treatment of estrogen receptor-positive breast cancer". International Journal of Oncology 28, no. 6 (2006): 1429-1439. https://doi.org/10.3892/ijo.28.6.1429