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Zymogen granule protein 16B (ZG16B) is a druggable epigenetic target to modulate the mammary extracellular matrix.
Cancer Sci
January 2025
Department of Clinical Oncology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary.
High tissue density of the mammary gland is considered a pro-tumorigenic factor, hence suppressing the stimuli that induce matrix buildup carries the potential for cancer interception. We found that in non-malignant mammary epithelial cells the combination of the chemopreventive agents bexarotene (Bex) and carvedilol (Carv) suppresses the zymogen granule protein 16B (ZG16B, PAUF) through an interaction of ARID1A with a proximal enhancer. Bex + Carv also reduced ZG16B levels in vivo in normal breast tissue and MDA-MB231 tumor xenografts.
View Article and Find Full Text PDFIRX4204 Induces Senescence and Cell Death in HER2-positive Breast Cancer and Synergizes with Anti-HER2 Therapy.
Clin Cancer Res
June 2024
Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Purpose: Rexinoids, agonists of nuclear retinoid X receptor (RXR), have been used for the treatment of cancers and are well tolerated in both animals and humans. However, the usefulness of rexinoids in treatment of breast cancer remains unknown. This study examines the efficacy of IRX4204, a highly specific rexinoid, in breast cancer cell lines and preclinical models to identify a biomarker for response and potential mechanism of action.
View Article and Find Full Text PDFPhase I Dose Escalation Study of Topical Bexarotene in Women at High Risk for Breast Cancer.
Cancer Prev Res (Phila)
January 2023
Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Bexarotene is a rexinoid that has been shown to prevent mammary tumors in mouse models but oral dosing has toxicities. This phase I study evaluates topical bexarotene, as a potential chemoprevention agent, for safety and toxicity in high-risk women for breast cancer.
View Article and Find Full Text PDFRedistribution of the SWI/SNF Complex Dictates Coordinated Transcriptional Control over Epithelial-Mesenchymal Transition of Normal Breast Cells through TGF-β Signaling.
Cells
August 2022
Department of Clinical Oncology, Faculty of Medicine, University of Debrecen, 4032 Debrecen, Hungary.
Therapeutic targets in cancer cells defective for the tumor suppressor ARID1A are fundamentals of synthetic lethal strategies. However, whether modulating ARID1A function in premalignant breast epithelial cells could be exploited to reduce carcinogenic potential remains to be elucidated. In search of chromatin-modulating mechanisms activated by anti-proliferative agents in normal breast epithelial (HME-hTert) cells, we identified a distinct pattern of genome-wide H3K27 histone acetylation marks characteristic for the combined treatment by the cancer preventive rexinoid bexarotene (Bex) and carvedilol (Carv).
View Article and Find Full Text PDFThe rexinoid V-125 reduces tumor growth in preclinical models of breast and lung cancer.
Sci Rep
January 2022
Department of Pharmacology and Toxicology, Michigan State University College of Osteopathic Medicine, B430 Life Science Building, 1355 Bogue Street, East Lansing, MI, 48824, USA.
Rexinoids are ligands which activate retinoid X receptors (RXRs), regulating transcription of genes involved in cancer-relevant processes. Rexinoids have anti-neoplastic activity in multiple preclinical studies. Bexarotene, used to treat cutaneous T cell lymphoma, is the only FDA-approved rexinoid.
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