To block or not to block - hormonal signaling in the treatment of cancers

Sep 24, 2026

Uploaded by moss~

Hormonal dependence drives endocrine therapy in breast and prostate cancers, yet deprivation strategies commonly lead to resistance and eventual hormone independence. This mini review explains how steroid hormones are produced through the HPG axis, how nuclear hormone receptors regulate gene transcription, and how non-canonical/non-genomic signaling and cross-talk can sustain proliferative, inflammatory, and immune-related processes. It further highlights why considering opposite-sex hormone signaling may support combinatorial treatment strategies, especially for prostate cancer.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages7

Reading Time18 min

AccessFree to download

Hormonal dependence and endocrine therapy context

Steroid hormone biosynthesis via the HPG axis

Nuclear hormone receptor signaling: genomic and non-genomic modes

Implications for resistance and combinatorial regimes

TYPE Mini Review PUBLISHED 20 February 2023 DOI 10.3389/fendo.2023.1129332 OPEN ACCESS EDITED BY Anna Perri, Magna Græcia University of Catanzaro, Italy REVIEWED BY Philipp Maximov, University of Texas MD Anderson Cancer Center, United States *CORRESPONDENCE Prathibha Ranganathan [pranganathan@chg. res.in](pranganathan@chg. res.in) SPECIALTY SECTION This article was submitted to Cancer Endocrinology, a section of the journal Frontiers in Endocrinology RECEIVED 21 December 2022 ACCEPTED 30 January 2023 PUBLISHED 20 February 2023 CITATION Abikar A, Saimon C and Ranganathan P (2023) To block or not to block—hormonal signaling in the treatment of cancers. Front. Endocrinol. 14:1129332 . doi: 10.3389/fendo.2023.1129332 COPYRIGHT © 2023 Abikar, Saimon and Ranganathan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. To block or not to block—hormonal signaling in the treatment of cancers Apoorva Abikar, Chriswin Saimon and Prathibha Ranganathan* Centre for Human Genetics, Bengaluru, India The breast and prostate glands are the two major organs that are highly dependent on the gonadal steroid hormones for their development and homeostasis. The cancers of these organs also show a large dependence on steroid hormones and have formed the basis of endocrine therapy . Estrogen deprivation by oophorectomy has been in active practice since the 1970s, and androgen deprivation therapy for prostate cancer was a major breakthrough in medicine in 1941. Since then, several improvisations have happened in these modes of therapy. However, the development of resistance to this deprivation and the emergence of hormone independence are major problems in both cancers. The lessons learned from rodent models have made it clear that the male hormone has a role in females and vice versa. Also, the metabolic products of these hormones may have unintentional effects including proliferative conditions in both sexes. Hence, administering estrogen as a method of chemical castration in males and administering DHT in females may not be the ideal scenario. It would be important to consider the status of the opposite sex hormone signaling and its effects and come up with a combinatorial regime to strike a balance between androgen and estrogen signaling. This review summarizes the current understanding and developments in this ﬁeld in the context of prostate cancer. KEYWORDS endocrine therapies, steroid hormones, tumor microenvironment, cell speciﬁc effects, mouse models, altered metabolism Nuclear hormone receptors are intracellular receptors that are activated by lipid-soluble ligands such as steroid hormones. Once bound by the ligand, most receptors function as transcription factors to control gene expression affecting numerous biological processes (reviewed in (1)) . Steroid hormones are derivatives of cholesterol and have a wide variety of physiological functions. These are classiﬁed based on the site of synthesis. The hormones which are synthesized by the gonads, both in males and females, are called gonadal steroids or sex hormones. Gonadal steroid hormone synthesis is mainly regulated by the hypothalamic– pituitary–gonadal (HPG) axis. The release of gonadotropin-releasing hormone (GnRH) from the hypothalamus results in the release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the pituitary into general circulation. The binding of LH to its receptors on Leydig cells in males and on theca cells in females causes the enhanced expression of the steroidogenic acute regulatory protein (StAR) .

FAQs

Why is hormonal signaling central to endocrine therapy in cancers?

Breast and prostate cancers depend strongly on gonadal steroid hormones, which is the biological basis of endocrine therapy.

What problem arises after estrogen or androgen deprivation?

Resistance to hormone deprivation and the emergence of hormone independence become major challenges in both cancers.

How can non-canonical or non-genomic nuclear hormone signaling affect disease progression?

Non-canonical actions, including cross-talk with other pathways, can promote proliferative, inflammatory, and immune-related processes and may contribute to resistance to endocrine therapies.

Sep 24, 2026

Uploaded by moss~