Discovery and development of steroidal enzyme inhibitors as anti-cancer drugs: state-of-the-art and future perspectives

Steroidal compounds have emerged as effective therapeutic agents in oncology. Beyond natural-occurring and synthetic steroids that act as cytotoxic anti-tumoral agents, steroidal derivatives can be designed to mime the endogenous substrates of key metabolic enzymes in steroidogenesis, thus reducing...

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Main Authors: Bruno Cerra, Antimo Gioiello
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Journal of Enzyme Inhibition and Medicinal Chemistry
Subjects:
Online Access:https://www.tandfonline.com/doi/10.1080/14756366.2025.2483818
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author Bruno Cerra
Antimo Gioiello
author_facet Bruno Cerra
Antimo Gioiello
author_sort Bruno Cerra
collection DOAJ
description Steroidal compounds have emerged as effective therapeutic agents in oncology. Beyond natural-occurring and synthetic steroids that act as cytotoxic anti-tumoral agents, steroidal derivatives can be designed to mime the endogenous substrates of key metabolic enzymes in steroidogenesis, thus reducing the circulating levels of relevant oestrogenic and androgenic hormones responsible for cancer survival and proliferation. Therefore, enzyme inhibition represents an intriguing endocrine approach for the treatment of hormone-dependent tumours, such as breast and prostate cancer, with well-known approved drugs and several pre-clinical and clinical candidates under investigation. This review summarises the key advancements over the past decade (2014–2024) in the development of steroidal enzyme inhibitors endowed with anticancer activity, illustrating their mechanisms of action, therapeutic potential, drug design approaches, and current clinical applications. Furthermore, we discuss challenges related to drug resistance, off-target effects, and future strategies to optimise their efficacy in oncology.
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spelling doaj-art-ea87579f6f5f42b3b2a1e7eab6ffa0112025-08-20T01:55:21ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742025-12-0140110.1080/14756366.2025.2483818Discovery and development of steroidal enzyme inhibitors as anti-cancer drugs: state-of-the-art and future perspectivesBruno Cerra0Antimo Gioiello1Department of Pharmaceutical Sciences, University of Perugia, Perugia, ItalyDepartment of Pharmaceutical Sciences, University of Perugia, Perugia, ItalySteroidal compounds have emerged as effective therapeutic agents in oncology. Beyond natural-occurring and synthetic steroids that act as cytotoxic anti-tumoral agents, steroidal derivatives can be designed to mime the endogenous substrates of key metabolic enzymes in steroidogenesis, thus reducing the circulating levels of relevant oestrogenic and androgenic hormones responsible for cancer survival and proliferation. Therefore, enzyme inhibition represents an intriguing endocrine approach for the treatment of hormone-dependent tumours, such as breast and prostate cancer, with well-known approved drugs and several pre-clinical and clinical candidates under investigation. This review summarises the key advancements over the past decade (2014–2024) in the development of steroidal enzyme inhibitors endowed with anticancer activity, illustrating their mechanisms of action, therapeutic potential, drug design approaches, and current clinical applications. Furthermore, we discuss challenges related to drug resistance, off-target effects, and future strategies to optimise their efficacy in oncology.https://www.tandfonline.com/doi/10.1080/14756366.2025.2483818Anticancer steroidsbreast cancerenzyme inhibitorsprostate cancersteroidogenesis inhibitors
spellingShingle Bruno Cerra
Antimo Gioiello
Discovery and development of steroidal enzyme inhibitors as anti-cancer drugs: state-of-the-art and future perspectives
Journal of Enzyme Inhibition and Medicinal Chemistry
Anticancer steroids
breast cancer
enzyme inhibitors
prostate cancer
steroidogenesis inhibitors
title Discovery and development of steroidal enzyme inhibitors as anti-cancer drugs: state-of-the-art and future perspectives
title_full Discovery and development of steroidal enzyme inhibitors as anti-cancer drugs: state-of-the-art and future perspectives
title_fullStr Discovery and development of steroidal enzyme inhibitors as anti-cancer drugs: state-of-the-art and future perspectives
title_full_unstemmed Discovery and development of steroidal enzyme inhibitors as anti-cancer drugs: state-of-the-art and future perspectives
title_short Discovery and development of steroidal enzyme inhibitors as anti-cancer drugs: state-of-the-art and future perspectives
title_sort discovery and development of steroidal enzyme inhibitors as anti cancer drugs state of the art and future perspectives
topic Anticancer steroids
breast cancer
enzyme inhibitors
prostate cancer
steroidogenesis inhibitors
url https://www.tandfonline.com/doi/10.1080/14756366.2025.2483818
work_keys_str_mv AT brunocerra discoveryanddevelopmentofsteroidalenzymeinhibitorsasanticancerdrugsstateoftheartandfutureperspectives
AT antimogioiello discoveryanddevelopmentofsteroidalenzymeinhibitorsasanticancerdrugsstateoftheartandfutureperspectives