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Aryl hydrocarbon receptor as a drug target in advanced prostate cancer therapy obstacles and perspectives
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SYSNO ASEP 0603284 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Aryl hydrocarbon receptor as a drug target in advanced prostate cancer therapy obstacles and perspectives Author(s) Procházková, Jiřina (BFU-R) RID, ORCID
Kahounová, Zuzana (BFU-R) ORCID
Vondráček, Jan (BFU-R) RID, ORCID
Souček, Karel (BFU-R) RID, ORCIDNumber of authors 4 Source Title Transcription-Austin. - : Taylor and Francis - ISSN 2154-1264
„neuveden“, „neuveden“ (2024)Number of pages 20 s. Language eng - English Country US - United States Keywords regulatory t-cells ; Aryl hydrocarbon receptor ; lactational 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure ; polycyclic aromatic-hydrocarbons ; ah-receptor ; in-utero ; androgen receptor ; suppressor-cells ; cross-talk ; hepatic-fibrosis ; double-blind ; prostate cancer ; castration resistance ; antibody-drug conjugates OECD category Biochemistry and molecular biology R&D Projects GA21-11585S GA ČR - Czech Science Foundation (CSF) Method of publishing Limited access Institutional support BFU-R - RVO:68081707 UT WOS 001194216100001 EID SCOPUS 85189646965 DOI https://doi.org/10.1080/21541264.2024.2334106 Annotation Aryl hydrocarbon receptor (AhR) is a transcription factor that is primarily known as an intracellular sensor of environmental pollution. After five decades, the list of synthetic and toxic chemicals that activate AhR signaling has been extended to include a number of endogenous compounds produced by various types of cells via their metabolic activity. AhR signaling is active from the very beginning of embryonal development throughout the life cycle and participates in numerous biological processes such as control of cell proliferation and differentiation, metabolism of aromatic compounds of endogenous and exogenous origin, tissue regeneration and stratification, immune system development and polarization, control of stemness potential, and homeostasis maintenance. AhR signaling can be affected by various pharmaceuticals that may help modulate abnormal AhR signaling and drive pathological states. Given their role in immune system development and regulation, AhR antagonistic ligands are attractive candidates for immunotherapy of disease states such as advanced prostate cancer, where an aberrant immune microenvironment contributes to cancer progression and needs to be reeducated. Advanced stages of prostate cancer are therapeutically challenging and characterized by decreased overall survival (OS) due to the metastatic burden. Therefore, this review addresses the role of AhR signaling in the development and progression of prostate cancer and discusses the potential of AhR as a drug target for the treatment of advanced prostate cancer upon entering the phase of drug resistance and failure of first-line androgen deprivation therapy.Abbreviation: ADC: antibody-drug conjugate, ADT: androgen deprivation therapy, AhR: aryl hydrocarbon receptor, AR: androgen receptor, ARE: androgen response element, ARPI: androgen receptor pathway inhibitor, mCRPC: metastatic castration-resistant prostate cancer, DHT: 5a-dihydrotestosterone, FICZ: 6-formylindolo[3,2-b]carbazole, 3-MC: 3-methylcholanthrene, 6-MCDF: 6-methyl-1,3,8-trichlorodibenzofuran, MDSCs: myeloid-derived suppressor cells, PAHs: polycyclic aromatic hydrocarbons, PCa: prostate cancer, TAMs: tumor-associated macrophages, TF: transcription factor, TCDD, 2,3,7,8-tetrachlorodibenzo-p-dioxin, TME: tumor microenvironment, TRAMP: transgenic adenocarcinoma of the mouse prostate, TROP2: tumor associated calcium signal transducer 2 Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2025 Electronic address https://www.tandfonline.com/doi/full/10.1080/21541264.2024.2334106
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