title: Estrogen enhances the efficacy of an oncolytic HSV-1 mutant in the treatment of estrogen receptor-positive breast cancer.
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.
authors: Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
authors: Brendon M
authors: BM
authors: Stiles
authors: Prasad S
authors: PS
authors: Adusumilli
authors: Stephen F
authors: SF
authors: Stanziale
authors: David P
authors: DP
authors: Eisenberg
authors: Amit
authors: A
authors: Bhargava
authors: Teresa H
authors: TH
authors: Kim
authors: Mei-Ki
authors: MK
authors: Chan
authors: Rumana
authors: R
authors: Huq
authors: Mithat
authors: M
authors: Gonen
authors: Yuman
authors: Y
authors: Fong