Abstract P5-19-05: Combination vorinostat and lapatinib reverses epithelial-mesenchymal transition, inhibits the cancer stem cell population of HER2+ breast cancer cells and is effective in heavily pretreated advanced tumors

Although strides have been made in the treatment of breast cancer, patients often relapse due to recurrence or metastasis. The targeting of these cellular processes has become essential in the quest for a cancer cure. Previously, we have demonstrated the efficacy of histone deacetylase inhibitors (HDACi) in inducing differentiation and inhibiting metastasis in triple negative breast cancer cells. In addition, we have shown that HER2 regulates the cancer stem cell (CSC) population in AI resistant cells. Based on these previous results, we hypothesize that the combination of both HDACi and HER2 inhibition may be synergistic and further reduce CSC. In this study, we treated a panel of HER2+ breast cancer cell lines with the combination of 1µM vorinostat (HDACi) and 1µM lapatinib (a dual EGFR/HER2 inhibitor) for 72 hours and examined its effects on cell number, mesenchymal and epithelial markers, migratory potential, and cancer stem cell characteristics. The combination reduced cell number when compared to either agent alone (p Citation Format: Amanda J Schech, Saranya Chumsri, Preeti Shah, Stephen L Yu, Nancy S Tait, Kenneth S Bauer, Jane C Lewis, Ting Bao, Martin J Edelman, Katherine H Tkaczuk, Angela H Brodie. Combination vorinostat and lapatinib reverses epithelial-mesenchymal transition, inhibits the cancer stem cell population of HER2+ breast cancer cells and is effective in heavily pretreated advanced tumors [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-19-05.