Targeting the formation of estrogens for treatment of hormone dependent diseases–current status

Frontiers in Pharmacology

Pharmacology

Andrea Romano¹  Tea Lanišnik Rižner² 

[1] GROW Department of Gynaecology, Faculty of Health, Medicine and Life Sciences (FHML)/GROW-School for Oncology and Reproduction, Maastricht University, Maastricht, Netherlands;Laboratory for Molecular Basis of Hormone-Dependent Diseases and Biomarkers, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia;

关键词: intracrinology;    estrogens;    breast cancer;    ovarian cancer;    endometrial cancer;    endometriosis;    prostate cancer;   

DOI  :  10.3389/fphar.2023.1155558

 received in 2023-01-31, accepted in 2023-04-10,  发布年份 2023

来源: Frontiers

【 摘 要 】

Local formation and action of estrogens have crucial roles in hormone dependent cancers and benign diseases like endometriosis. Drugs that are currently used for the treatment of these diseases act at the receptor and at the pre-receptor levels, targeting the local formation of estrogens. Since 1980s the local formation of estrogens has been targeted by inhibitors of aromatase that catalyses their formation from androgens. Steroidal and non-steroidal inhibitors have successfully been used to treat postmenopausal breast cancer and have also been evaluated in clinical studies in patients with endometrial, ovarian cancers and endometriosis. Over the past decade also inhibitors of sulfatase that catalyses the hydrolysis of inactive estrogen-sulfates entered clinical trials for treatment of breast, endometrial cancers and endometriosis, with clinical effects observed primarily in breast cancer. More recently, inhibitors of 17beta-hydroxysteroid dehydrogenase 1, an enzyme responsible for formation of the most potent estrogen, estradiol, have shown promising results in preclinical studies and have already entered clinical evaluation for endometriosis. This review aims to provide an overview of the current status of the use of hormonal drugs for the major hormone-dependent diseases. Further, it aims to explain the mechanisms behind the -sometimes- observed weak effects and low therapeutic efficacy of these drugs and the possibilities and the advantages of combined treatments targeting several enzymes in the local estrogen formation, or drugs acting with different therapeutic mechanisms.

【 授权许可】

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Copyright © 2023 Rižner and Romano.