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Antitumor benzothiazoles, including 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203; NSC 703786), non-fluorinated parent compound DF 203 (NSC 674495), and Phortress (NSC 710305), the lysyl amide prodrug of 5F 203, are experimental anticancer agents with activity in ovarian and breast cancer models in vitro and in vivo. These compounds require (and induce their own) metabolism by cytochrome P450 (CYP) enzymes (e.g., CYP1A1) for antitumor action. The aryl hydrocarbon receptor (AhR) is the main transcriptional regulator of CYP1A1, and we have previously demonstrated that DF 203 and 5F 203 are potent AhR ligands and trigger activation of AhR signaling in sensitive breast and ovarian cancer cells, causing nuclear translocation of AhR. We propose that AhR may represent a new molecular target in the treatment of ovarian tumors, and 5F 203 may exemplify a potential novel treatment. Furthermore, putative biomarkers of sensitivity to this agent have been identified.

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Exploring New Molecular Targets in Advanced Ovarian Cancer: The Aryl Hydrocarbon Receptor (AhR) and Antitumor Benzothiazole Ligands as Potential Therapeutic Candidates