Over 75% of breast cancer tumors are dependent on estrogen for their growth. Commonly used antihormonal therapeutics block the binding of estrogen to its receptor or block the conversion of precursor hormones to estrogen. While these drugs are active, many women may not respond to therapy. Several studies have suggested that the addition of a novel class of drugs called the histone deacetylase (HDAC) inhibitors may improve the antitumor effects of tamoxifen. However, the HDAC inhibitors may inhibit several HDAC enzymes, and very little is known whether certain HDAC enzymes are more important than others. Furthermore, it is not known which HDAC enzymes may affect antihormonal therapy.
In this proposal, we will determine how the inhibition of specific HDAC enzymes may affect the response to antihormonal therapy. In Aim 1, we will study the roles of specific HDAC enzymes in breast cancer cell culture models. In Aim 2, we will determine whether specific HDAC enzymes predict response by evaluating the estrogen receptor and HDAC expression patterns in banked tumor tissues from patients that were treated with a combination of the HDAC inhibitor, vorinostat, and tamoxifen. These studies will help determine which patients are most likely to benefit from a combination of HDAC inhibitors and antihormonal therapy. |
