%0 Journal Article
%T Bile Acid Receptor FXR Agonism with Ocaliva Reduces Tumor Burden and MYC Signaling in Preclinical TNBC
%A I. Popovici
%A C. Dumitru
%A V. Munteanu
%J Asian Journal of Current Research in Clinical Cancer
%@ 3062-4444
%D 2025
%V 5
%N 1
%R 10.51847/Kv9qA56ngW
%P 81-92
%X Bariatric procedures have been linked to better prognoses in several cancers, including breast cancer (BC), though the biological drivers of this benefit remain unclear. We proposed that the rise in circulating bile acids observed after bariatric surgery could play a role in enhanced BC outcomes. Individuals whose tumors showed elevated levels of the bile acid-responsive receptor FXR had improved survival in specific aggressive BC phenotypes. FXR, a nuclear receptor activated primarily by endogenous bile acids, was therefore selected as a therapeutic target. We hypothesized that stimulating FXR with an FDA-approved agonist might yield anti-neoplastic effects. Using both cell-based systems and animal models, we assessed whether pharmacological activation of FXR suppresses tumor behavior. Administration of the bile acid analog Obeticholic acid (OCA; INT-747; commercially “Ocaliva”) markedly curtailed tumor growth and overall disease burden in a preclinical BC setting. Transcriptomic profiling of OCA-treated mouse tumors uncovered distinct gene expression differences relative to controls, including a notable reduction in MAX (MYC-associated factor X), a transcription factor that cooperates with MYC. Gene set enrichment analysis (GSEA) confirmed a significant suppression of the Hallmark MYC Target V1 gene ensemble following OCA exposure. Across multiple human and murine BC cell lines, FXR stimulation produced dose-dependent decreases in proliferation, motility, and cell viability. By contrast, synthetic activation of TGR5 (GPBAR1), another common bile acid receptor responsive mainly to secondary bile acids, showed no meaningful influence on cancer cell behavior. Altogether, activating FXR with a primary-bile-acid mimetic such as OCA exerts strong anti-tumor activity, seemingly by limiting growth and migration while reducing viability. These data highlight FXR as a potential tumor-suppressive target with relevance for personalized BC therapies.
%U https://galaxypub.co/article/bile-acid-receptor-fxr-agonism-with-ocaliva-reduces-tumor-burden-and-myc-signaling-in-preclinical-tn-5mnyan2l2gpzvnj