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Steroid sulfatase inhibitors for estrogen- and androgen-dependent cancers
Open accessAbstract
Estrogens and androgens are instrumental in the maturation of many hormone-dependent cancers. Consequently, the enzymes involved in their synthesis are cancer therapy targets. One such enzyme, steroid sulfatase (STS), hydrolyses estrone sulfate, and dehydroepiandrosterone sulfate to estrone and dehydroepiandrosterone respectively. These are the precursors to the formation of biologically active estradiol and androstenediol. This review focuses on three aspects of STS inhibitors: 1) chemical development, 2) biological activity, and 3) clinical trials. The aim is to discuss the importance of estrogens and androgens in many cancers, the developmental history of STS inhibitor synthesis, the potency of these compounds in vitro and in vivo and where we currently stand in regards to clinical trials for these drugs. STS inhibitors are likely to play an important future role in the treatment of hormone-dependent cancers. Novel in vivo models have been developed that allow pre-clinical testing of inhibitors and the identification of lead clinical candidates. Phase I/II clinical trials in postmenopausal women with breast cancer have been completed and other trials in patients with hormone-dependent prostate and endometrial cancer are currently active. Potent STS inhibitors should become therapeutically valuable in hormone-dependent cancers and other non-oncological conditions.
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“including STX64, which was effective in blocking synthesis in endometrial cancer cells in vitro.”
From Endometrial Intracrinology: Oestrogens, Androgens and Endometrial Disorders (2018) · cites this paper as [107]
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“The potential of STS inhibition has been evaluated in promising clinical trials (Geisler et al., 2011, Purohit and Foster, 2012, Thomas and Potter, 2015).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Purohit and Foster, 2012
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The Regulation of Steroid Action by Sulfation and Desulfation
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Metadata
- Authors
- Purohit, A., & Foster, P. A.
- Affiliations
- Hammersmith Hospital (GB)
- ORCID
- Foster, Paul A
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2011-08-22
- Volume
- 212
- Issue
- 2
- Pages
- 99-110
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2143089038
- Cited by
- 126
- References
- 105
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 2 · 2023: 7 · 2022: 5 · 2021: 8 · 2020: 5 · 2019: 12 · 2018: 11 · 2017: 11 · 2016: 14 · 2015: 12 · 2014: 16 · 2013: 11 · 2012: 6
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
- Funders
- Ipsen
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Physical Sciences › Chemistry › Organic Chemistry › Steroid Chemistry and Biochemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Keywords
- steroid sulfatase inhibitors, steroid sulfatase, estrone sulfate, dehydroepiandrosterone sulfate, hormone-dependent tumors, breast cancer, prostate cancer, endometrial cancer, estrogen metabolism, androgen metabolism, drug development, clinical trials, postmenopausal women
- MeSH terms
- Androgens, Animals, Breast Neoplasms, Enzyme Inhibitors, Estrogens, Female, Humans, Male, Neoplasm Proteins, Neoplasms, Hormone-Dependent, Prostatic Neoplasms, Receptors, Androgen, Receptors, Estrogen, Antineoplastic Agents, Hormonal, Steryl-Sulfatase, Aromatase Inhibitors, Molecular Targeted Therapy
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