Abstract C054: Pharmacogenomics evaluation of histone deacetylase inhibitors on the treatment of triple-negative breast cancer subtypes

Triple-negative breast cancer (TNBC) is an aggressive breast cancer type with very few effective treatment options, prone to recurrence and metastasis, and has poor prognosis in affected patients. This cancer is characterized by a lack of estrogen, progesterone, and human epidermal growth factor receptor 2 receptors; thus, it does not respond to targeted therapies or therapeutic treatments that target these receptors. Current treatment of TNBC includes the use of poly (ADP-ribose) polymerase (PARP). However, long-term challenges remain with the use of PARP inhibitors, such as primary and secondary resistance to the drugs. Hence, there’s urgent need to evaluate novel therapeutics, such as Vorinostat, in treating TBNC. Vorinostat, a histone deacetylase inhibitor, approved by the US Food and Drug Administration for the treatment of cutaneous T cell lymphoma, has been studied for its ability to treat other cancer types, including in combination with other therapeutics with promising results. Previous studies have demonstrated diverse responses to treatment with Vorinostat in TNBC subtypes. Here, we show that Vorinostat inhibits the proliferation and viability of racially diverse TBNC subtypes in a dose-and-time-dependent manner. Using Matrigel-based migration assay, Vorinostat suppresses the invasive nature of racially diverse TBNC subtypes. Currently, we are examining the effect of Vorinostat on the activity of specific classes of histone deacetylase as well as identifying biomarkers of efficacy and drug-gene interactions across the racially diverse TNBC subtypes. This research provides data on the efficacy, safety, and underlying mechanisms employed by the drug to execute its therapeutic responses. Citation Format: Bright Obeng, Kelly Harris, Beverly Lyn-cook, Beverly Word. Pharmacogenomics evaluation of histone deacetylase inhibitors on the treatment of triple-negative breast cancer subtypes [abstract]. In: Proceedings of the 18th AACR Conference on the Science of Cancer Health Disparities; 2025 Sep 18-21; Baltimore, MD. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2025;34(9 Suppl):Abstract nr C054.