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

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

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1429-1439
Number of pages11
JournalInternational Journal of Oncology
Issue number6
StatePublished - Jun 2006
Externally publishedYes


  • Apoptosis
  • Bcl-2
  • Herpes simplex
  • Hormonal therapy
  • Replication-competent viruses


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