Abstract P5-12-12: The role of a cancer testis-antigen in regulating tumor growth and oncogenic pathways in triple-negative breast cancer

Abstract

Abstract Breast cancer is the second leading cause of cancer mortality in women after lung cancer; however, it is the primary cause of death among Hispanic women. About 10-20% of breast cancers are basal (triple-negative) subtype at the time of diagnosis, and they do not respond well to treatment regimens due to a lack of specific targets. Triple-negative breast cancer is a deadly and very aggressive tumor type associated with poor prognosis compared to other molecular subtypes of breast cancer, especially among Hispanic women. Thus, identifying novel molecules with prognostic and therapeutic value is critical to treat this ever-evolving disease. Numerous studies suggest that genes transcribed from chromosome X (X-linked genes) are implicated in cancers. The expression of these genes is tightly regulated and restricted to immune-privileged organs; however, many of them escape regulation and become aberrantly expressed in tumors.Interestingly, our genomic analysis suggests that several newly annotated X-linked genes are cancer testis-antigens (CT genes) that are highly antigenic and are located at regions previously considered to be gene deserts in the human genome. To date, very minimal is known about their expression and role in triple-negative breast cancer. In this regard, we used an integrated genomic approach to identify testis-tissue-specific genes that are differentially expressed in triple-negative breast cancer. Further, we identified a highly immunogenic cancer-testis gene by incorporating cutting-edge technology-driven (Global Run-On Sequencing) gene expression analysis. Mechanistically, by using cell-, mouse-based, and genomic approaches, we have found that candidate CT gene modulates gene expression, immune response, and tumor growth in triple-negative breast cancer. Hence, it has the potential to change the way triple-negative breast cancer is diagnosed and treated. S.S.G. is supported by a First-time Faculty Recruitment Award from the Cancer Prevention and Research Institute of Texas (CPRIT; RR170020). S.S.G. is also supported by a grant from Lizanell and Colbert Coldwell foundation. Citation Format: Melina J Sedano, Alana L Harrison, Ine le, Shrikanth S Gadad. The role of a cancer testis-antigen in regulating tumor growth and oncogenic pathways in triple-negative breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-12-12.