New
therapies are needed for metastatic
breast cancer patients. Oncolytic herpes simplex virus (oHSV) is an exciting
therapy being developed for use against aggressive
tumors and established
metastases. Although oHSV have been demonstrated safe in clinical trials, a lack of sufficient potency has slowed the clinical application of this approach. We utilized
histone deacetylase (
HDAC) inhibitors, which have been noted to impair the innate
antiviral response and improve gene transcription from viral vectors, to enhance the replication of oHSV in
breast cancer cells. A panel of chemically diverse
HDAC inhibitors were tested at three different doses (<, = , and >LD50) for their ability to modulate the replication of oHSV in
breast cancer cells. Several of the tested
HDAC inhibitors enhanced oHSV replication at low multiplicity of
infection (MOI) following pre-treatment of the metastatic
breast cancer cell line MDA-MB-231 and the oHSV-resistant cell line 4T1, but not in the normal breast epithelial cell line MCF10A. Inhibitors of class I HDACs, including pan-selective compounds, were more effective for increasing oHSV replication compared to inhibitors that selectively target class II HDACs. These studies demonstrate that select
HDAC inhibitors increase oHSV replication in
breast cancer cells and provides support for pre-clinical evaluation of this combination strategy.