Abstract 6378: CDC20 is a novel therapeutic target in triple-negative breast cancer

Abstract

Background: Approximately 15% of breast cancers lack expression of Estrogen Receptor (ER), Progesterone Receptor (PR) and Human Epidermal Growth Factor Receptor 2 (HER-2), and are referred to as Triple-Negative Breast Cancer (TNBC). Due to a lack of targeted therapies, clinical outcomes in patients with TNBC continue to be poor. Likewise, due to the inherently aggressive biology of the disease, patients are forced to deal with the toughest breast cancer while having the least treatment options. In this study, we identified Cell Division Cycle protein 20 (CDC20), a key regulatory protein that mediates sister chromatid separation in mitosis, as a novel therapeutic target in TNBC. Methods: To uncover new drivers of TNBC, we nominated genes that are significantly overexpressed in patients with TNBC, compared to non-TNBCs. After identifying CDC20 as a top hit in this analysis, we used RNAseq analyses, expression microarrays, and Western blotting to assess CDC20 expression levels in breast cancer patients and cell lines. Kaplan-Meier analyses were formed to study the correlation between clinical outcomes and CDC20 expression levels, including recurrence-free survival, metastasis-free survival and overall survival. shRNA and siRNA-mediated knockdown of CDC20 in TNBC cell lines were employed to study the role of CDC20 in TNBC proliferation, invasion, and migration. Results: CDC20 was significantly overexpressed in TNBCs (compared to non-TNBCs) patients and is a predictor of poor clinical outcomes and radiation resistance. CDC20 expression was also significantly higher in TNBC cell lines compared to non-TNBC cell lines, reflecting what is seen in clinical data sets, such as in The Cancer Genome Atlas. Sh and siRNA-mediated knockdown of CDC20 expression resulted in decreased proliferation, invasion and migration in TNBC cell lines. Conclusions and future directions: Our findings support the development of pharmacologic strategies to inhibit CDC20 function as a potential targeted therapy against TNBC. Efforts are underway to validate our findings in vivo in xenograft models of TNBC in mice. Citation Format: Jayesh K. Sharma, Prasanna Alluri, Nashir Udden. CDC20 is a novel therapeutic target in triple-negative breast cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6378.