Sulfatase and aromatase pathway (Homo sapiens)

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The intratumoral production of E2 from circulating steroid hormone precursors plays an essential role in estrogen-related breast and endothelial ovarian cancer (EOC). There are two possible pathways producing E2, one being the sulfatase pathway starting from E1S, and one being the aromatase pathway which starts with DHEA-S. Both routes rely on two crucial enzymes: STS for estrogen activation and SULT1E1 for inactivation. Research indicates that an increased STS expression and E2 production is associated with cancer progression. However, sulfonation of E2 via SULT1E1 not only reduces proliferative effects of estrogens on hormone-sensitive tumor cells, but also generates water-soluble estrogen sulfates consequently leading to an increased excretion of sulfonated E2. This helps preventing a metabolic activation of the hormone into potentially mutagenic catechol metabolites. Thus, targeting estrogen-modifying enzymes in the sulfatase pathway is a potential endocrine therapy strategy for patients with estrogen-sensitive EOC. This pathway is based on Figure 1 from: Mungenast, F., Aust, S., Vergote, I., Vanderstichele, A., Sehouli, J., Braicu, E., Mahner, S., Castillo‑Tong, D. C., Zeillinger, R., Thalhammer, T."Clinical significance of the estrogen-modifying enzymes steroid sulfatase and estrogen sulfotransferase in epithelial ovarian cancer". Oncology Letters 13, no. 6 (2017): 4047-4054. https://doi.org/10.3892/ol.2017.5969