Abstract 3740: Ionizing radiation-induced transcriptomic changes in triple-negative breast cancer cells reveal putative mechanisms of treatment resistance

Abstract

Breast cancer is the most common malignancy and the second leading cause of cancer-associated deaths in women. Of these, triple-negative breast cancers (TNBCs) remain the most difficult to treat. Unlike hormone-driven breast cancers, TNBCs that remain in remission past the five-year mark rarely relapse and are considered functionally cured. Thus, investigating mechanisms of treatment resistance in order to improve remission rates is of paramount importance. In this study, we use RNA-Seq to analyze global transcriptomic changes in TNBC cells in response to DNA damage induced by ionizing radiation (IR). Applying gene set enrichment analysis (GSEA), we have identified a number of expression signatures that represent putative mechanisms of resistance to treatment. In prior work, we have demonstrated the role of the transcription factor Gli1, the terminal effector of the Hedgehog (Hh) signaling pathway, in regulating the expression of DNA repair proteins in response to genotoxic damage with cisplatin. We have previously shown that Hh inhibition blunts the expected upregulation of specific proteins involved in single-strand DNA repair in ovarian cancer cells. Here, we expand on our earlier studies by examining TNBC cells with high levels of Hh activity and querying how global transcriptomic changes in response to IR are altered by Hh inhibition. Our data suggest that rational manipulation of these pathways may sensitize TNBCs to treatment and improve the functional cure rate of these tumors. Citation Format: Victor T. Lin, Tshering D. Lama-Sherpa, Rajeev S. Samant, Lalita A. Shevde. Ionizing radiation-induced transcriptomic changes in triple-negative breast cancer cells reveal putative mechanisms of treatment resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3740.