Breast cancer is the most common tumor type in men and women combined; this year the National Cancer Institute estimates there will be 290,560 new cases in the United States and 43,780 deaths (2022). Triple Negative Breast Cancer (TNBC) lacks three typical surface markers of breast cancer-estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2)-which are common targets for endocrine or drug therapy, severely limiting TNBC treatment options. 40% of TNBC patients will die within five years of diagnosis (Yin 2020). Additionally, it has heightened risk for metastasis after neoadjuvant chemotherapy (defined as chemotherapy followed by surgical extraction of the tumor) compared to non-TNBC (Liedtke 2014) and the post-surgical recurrence rate of TNBC is as much as 25% (Yin 2020). The poor prognosis and low success rate of surgical treatment and chemotherapy underline the necessity of new treatment options. Discovery of new drugs would enable better treatment of TNBC and could greatly improve patient survival. Using a computational workflow, Automated Reproducible MOdular Workflow for Preprocessing and Differential Analysis of RNA-seq Data (ARMOR), we identified differentially expressed genes in TNBC cells. Publicly available RNA-sequencing files were obtained from the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database. ARMOR used RNA-sequencing data from high-throughput sequencing and massively parallel computing to map and quantify the sequencing reads from each clinical sample to the human transcriptome. We determined genes that are overexpressed or underexpressed compared to healthy cells. We then contextualized the genes identified by ARMOR into signaling pathways using SPIA (Signaling Pathway Impact Analysis). Our third software, Pathways2Targets contains a drug database and elucidates drugs that have known interactions with these enriched signaling pathways, ranking them based on how many pathways they can target. Our findings predicted existing, FDA-approved drugs that could be relevant therapeutics for TNBC, which can then be evaluated in future experiments and clinical trials. These results could improve survival rates and quality of life for patients with TNBC. Literature Cited:
Yin, L., Duan, J. J., Bian, X. W., & Yu, S. C. (2020). Triple-negative breast cancer molecular subtyping and treatment progress. Breast cancer research : BCR, 22(1), 61. https://doi.org/10.1186/s13058-020-01296-5 Hormone therapy for breast cancer: Breast cancer treatment. American Cancer Society. (n.d.). Retrieved October 31, 2022, from https://www.cancer.org/cancer/breast-cancer/treatment/hormone-therapy-for-breast-cancer.html.