Steroid sulfatase inhibitors for estrogen- and androgen-dependent cancers

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   Figure 1

   The origin of estrogenic steroids. Estrone sulfate (E₁S) is found circulating at high concentrations. STS, upregulated in many hormone-dependent cancers, causes peripheral tissue conversion of E₁S to estrone (E₁). E₁ is then reduced to estradiol (E₂) by 17β-HSD type 1, binds to the estrogen receptor (ER) and causes cell proliferation. AROM, aromatase; ST, sulfotransferase; STS, sulfatase; 17β-HSD, 17β-hydroxysteroid dehydrogenase; ER, estrogen receptor; DHEA, dehydroepiandrosterone; DHEA-ST, dehydroepiandrosterone sulfotransferase.
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   Figure 2

   The origin of androgenic steroids. Dehydroepiandrosterone (DHEA), synthesized from cholesterol in the adrenal gland, is sulfonated by DHEA sulfotransferase (DHEA-ST, also known as SULT2A1) to dehydroepiandrosterone sulfate (DHEAS) which is the most abundant circulating conjugated steroid. Local tissue conversion of DHEAS to DHEA is mediated by STS. Once unconjugated, DHEA is further metabolized to the active androgens, androstenediol, testosterone, and dihydrotestosterone that bind the androgen receptor (AR) leading to cell proliferation. AROM, aromatase; ST, sulfotransferase; STS, sulfatase; 17β-HSD, 17β-hydroxysteroid dehydrogenase; AR, androgen receptor.
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   Figure 3

   Examples of STS inhibitors.
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   Figure 4

   Examples of dual-targeting STS inhibitors.

• © 2012 Society for Endocrinology