17β-Hydroxysteroid Dehydrogenase Inhibition in Cancer Therapeutics
Summary
17β-Hydroxysteroid dehydrogenases (17β-HSDs) regulate intratumoral steroid hormone concentrations by catalysing interconversion of oestrogens and androgens. Type 1 isoform converts estrone (E1) to the biologically potent estradiol (E2), driving proliferation in oestrogen receptor–positive cancers, while type 2 mediates E2 oxidation, counteracting oestrogenic stimulation. Aberrant expression of 17β-HSD1 is implicated in disease progression and resistance to aromatase inhibitors, rendering it an attractive therapeutic target. Inhibition strategies encompass small-molecule antagonists, non-steroidal scaffolds and structure-guided designs aimed at selective blockade of hormone activation without disrupting systemic endocrine homeostasis. Recent advances in structural biology have refined active-site mapping, facilitating the development of compounds with nanomolar potency and isoform selectivity. Preclinical models demonstrate that 17β-HSD1 inhibitors can suppress tumour growth, restore androgenic antiproliferative signals and enhance sensitivity to existing endocrine therapies. Translational efforts continue to optimise pharmacokinetics, minimise off-target effects and validate biomarkers for patient stratification, underscoring the global importance of 17β-HSD inhibition in precision oncology.
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17β-Hydroxysteroid Dehydrogenase Inhibition in Cancer Therapeutics publication trend
The graph below shows the total number of articles in 17β-hydroxysteroid dehydrogenase inhibition in cancer therapeutics across all publications each year (not limited to Nature Index journals).
Technical terms
17β-Hydroxysteroid Dehydrogenases (17β-HSDs): A family of enzymes that regulate activation and inactivation of steroid hormones within tissues.
17β-HSD1: The isoform that reduces estrone (E1) to the more potent estradiol (E2), promoting oestrogen-dependent tumour growth.
17β-HSD2: The isoform that oxidises estradiol (E2) to estrone (E1), thus reducing oestrogenic stimulation.
Estradiol (E2): The most potent natural oestrogen, responsible for driving proliferation in hormone-sensitive cancers.
Estrone (E1): A less active form of oestrogen that serves as a substrate for 17β-HSD1.
IC50: The concentration of an inhibitor required to reduce enzyme activity by fifty per cent, indicating compound potency.
Dihydrotestosterone (DHT): A potent androgen that can exert antiproliferative effects in breast cancer when its inactivation is blocked.
References
- Chemical Synthesis and Biological Evaluation of 3-Substituted Estrone/Estradiol Derivatives as 17β-Hydroxysteroid Dehydrogenase Type 1 Inhibitors Acting via a Reverse Orientation of the Natural Substrate Estrone. Molecules (2023).
- Blocking oestradiol synthesis pathways with potent and selective coumarin derivatives. Journal of Enzyme Inhibition and Medicinal Chemistry (2018).
- Estrogen and androgen-converting enzymes 17β-hydroxysteroid dehydrogenase and their involvement in cancer: with a special focus on 17β-hydroxysteroid dehydrogenase type 1, 2, and breast cancer. Oncotarget (2017).
- 17beta-hydroxysteroid dehydrogenase type 1 stimulates breast cancer by dihydrotestosterone inactivation in addition to estradiol production.. Endocrinology (2010).
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