Abstract IA23: "NO Target for Cancer Stem Cells"

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Abstract Developing novel therapies that target cancer metastasis, chemoresistant cancer stem cells, and augment the efficacy of systemic chemo/radiotherapies is crucial to reducing cancer-associated mortality. A protein within the tumor microenvironment that has gained interest as a promising therapeutic target is nitric oxide synthase (NOS). Our previous findings have shown that increased inducible nitric oxide synthase (iNOS) expression is a poor prognostic indicator and associated with worse overall survival in triple negative breast cancer (TNBC) patients. Nitric oxide (NO) is a unique molecule in its ability to target multiple oncogenic pathways in a spatial and temporal manner, such as PI3K, extracellular signal-regulated kinase (ERK), β-catenin pathway, transforming growth factor beta (TGFβ) signaling, and hypoxia-inducible factor (HIF). Growing evidence has also suggested that hyperactivation of the phosphoinositide-3-kinase (PI3K) survival signaling pathway may be one of the most common oncogenic aberrations in certain TNBC subsets, in particular metaplastic breast cancer (MpBC). We will summarize the role of NO in PI3K-Akt pathway activation in human TNBC, as well as data from The Cancer Genome Atlas of the role of iNOS and PI3K-Akt interaction. This review discusses the current knowledge of the roles of nitric oxide (NO) in tumor progression and cancer metastasis, and promising preclinical studies that evaluated NOS inhibitors as an anti-cancer therapy. Lastly, we will offer a perspective on utilizing NOS inhibitors in the clinical setting, highlighting the prospects and outstanding challenges. Citation Format: Jenny C. Chang. "NO Target for Cancer Stem Cells" [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr IA23.