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Morris KT, Toth-Fejel S, Schmidt J, Fletcher WS, Pommier RF. High dehydroepiandrosterone-sulphate predicts breast cancer progression during new aromatase inhibitor therapy and stimulates breast cancer cell growth in tissue culture: a new role for adrenalectomy. Surgery 130, 947-953 (2001). Discusses the potential role of dehydroepiandrosterone sulfate in breast cancer progression on aromatase inhibitors (AIs).
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This neoadjuvant study demonstrated the upregulation of steroid sulfatase in tumors treated with an AI, which could serve as a potential compensatory mechanism to the depletion of intratrumoral estrogen, and therefore a mechanism of resistance to AI treatment
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Chanplakorn N, Chanplakorn P, Suzuki T et al. Increased estrogen sulfatase (STS) and 17β-hydroxysteroid dehydrogenase type 1(17β-HSD1) following neoadjuvant aromatase inhibitor therapy in breast cancer patients. Breast Cancer Res. Treat. 120, 639-648 (2010). This neoadjuvant study demonstrated the upregulation of steroid sulfatase in tumors treated with an AI, which could serve as a potential compensatory mechanism to the depletion of intratrumoral estrogen, and therefore a mechanism of resistance to AI treatment.
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Describes the synthesis and activity of a series of tricyclic 4-methylcoumarin-7-O-sulphamate (Coumate; later called irosustat). 667 Coumate (later called STX64) is the compound that subsequently entered a Phase I study and was later renamed irosustat
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Demonstrated that 667 Coumate caused the regression of estrone sulfate-stimulated tumor growth in a dose-dependent manner
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Purohit A, Woo LW, Potter BV, Reed MJ. In vivo inhibition of estrone sulfatase activity and growth of nitromethylurea-aromatized mammary tumours by 667 COUMATE. Cancer Res. 60, 3394-3396 (2000). Demonstrated that 667 Coumate caused the regression of estrone sulfate-stimulated tumor growth in a dose-dependent manner.
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First Phase I study of irosustat that revealed the potency of this agent as a sulfatase inhibitor and unexpectedly showed a decrease in androstenedione, revealing the importance of peripheral production
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Stanway SJ, Purohit A, Woo LW et al. Phase I Study of STX 64 (667 Coumate) in breast cancer patients: the first study of a steroid sulfatase inhibitor. Clin. Cancer Res. 12, 1585-1592 (2006). First Phase I study of irosustat that revealed the potency of this agent as a sulfatase inhibitor and unexpectedly showed a decrease in androstenedione, revealing the importance of peripheral production.
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