Chemotherapy resistance presents a major challenge in the treatment of triple negative breast cancer (TNBC), which is characterized by low or no expression of the estrogen receptor (ER), the progesterone receptor (PR), and the human epidermal growth factor receptor-2 (HER2). Because TNBC tumors do not express these receptors, there has been little to no advancement in the establishment of drug therapies to specifically target this breast cancer subtype. Additionally, unfavorable side effects and drug resistance reveal an urgent need for safer, more effective therapeutic options. In this study, we aim to mimic cancer recurrence by establishing doxorubicin (DOX) resistance in TNBC cell lines, HCC1806 and HCC70 and investigate the effect on cell survival, cell migration, and changes in gene expression. Here we show that TNBC cell growth was sustained after pulse treatments with increasing concentrations of DOX. HCC1806 and HCC70 cells treated with DOX titrants (0.5 µM-2.0 µM) demonstrate cell growth sustainability after 3h treatments. The DOX-treated TNBC cells also demonstrate anti-migratory potential. RNA sequencing analysis show that IL6, TP53, and TNFSF12 are uniquely expressed after 24h exposure to 0.5uM DOX. We plan to further investigate the roles these genes play in chemoresistance. Understanding changes in the gene network, as a result of doxorubicin-resistance, may help to establish biomarkers that could represent targets for drug therapies to overcome chemoresistance in TNBC.
Citation Format: Kashenya Pearson, Terrence Everett, Checo J. Rorie. Mimicking the evolution of doxorubicin resistance in triple negative breast cancer [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr B030.