The metabolism, analysis, and targeting of steroid hormones in breast and prostate cancer

Capper, Cameron P.; Rae, James M.; Auchus, Richard J.

doi:10.1007/s12672-016-0259-0

Cited by 90Prostate Cancer Treatment and ResearchEstrogen and related hormone effectsCancer, Lipids, and Metabolism

The metabolism, analysis, and targeting of steroid hormones in breast and prostate cancer

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Capper, Cameron P., Rae, James M., Auchus, Richard J.·2016·Hormones and Cancer

DOI 10.1007/s12672-016-0259-0PMC PMC4860032

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Abstract

Breast and prostate cancers are malignancies in which steroid hormones drive cellular proliferation. Over the past century, this understanding has led to successful treatment strategies aimed to inhibit hormone-mediated tumor growth. Nonetheless, disease relapse and progression still pose significant clinical problems, with recurrent and metastatic tumors often exhibiting resistance to current drug therapies. The central role of androgens and estrogens in prostate and breast cancer etiology explains not only why endocrine therapies are often initially successful but also why many tumors ultimately become resistant. It is hypothesized that reducing the concentration of active hormones in the systemic circulation may be insufficient to block cancer progression, as this action selects for tumor cells that can generate active steroids from circulating precursors. This review aims to highlight the currently known differences of steroid biosynthesis in normal physiology versus hormone-dependent cancers, modern approaches to the assessment and targeting of these pathways, and priorities for future research.

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CRPC is dependent on the intracrine conversion of circulating androgen precursors of adrenal origin to active androgens.
“numerous studies have shown that CRPC is dependent on the intracrine conversion of circulating androgen precursors of adrenal origin to active androgens reviewed in (Capper et al., 2016, Luu-The et al., 2008, Pretorius et al., 2017, Sharifi and Auchus, 2012).”
From Intracrine androgen biosynthesis, metabolism and action revisited (2018) · cites this paper as Capper et al., 2016

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Results from a phase 2 study of enzalutamide (ENZA), an androgen receptor (AR) inhibitor, in advanced AR+ triple-negative breast cancer (TNBC).
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ASSIGNMENT OF THE GENE FOR ADRENAL P450cl7 (STEROID 17α-HYDR0XYLASE⁄17,20 LYASE) TO HUMAN CHROMOSOME 10.
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Phase III, Randomized, Double-Blind, Multicenter Trial Comparing Orteronel (TAK-700) Plus Prednisone With Placebo Plus Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer That Has Progressed During or After Docetaxel-Based Therapy: ELM-PC 5
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Galeterone and VNPT55 induce proteasomal degradation of AR/AR-V7, induce significant apoptosis via cytochrome c release and suppress growth of castration resistant prostate cancer xenograftsin vivo
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Abiraterone Inhibits 3β-Hydroxysteroid Dehydrogenase: A Rationale for Increasing Drug Exposure in Castration-Resistant Prostate Cancer
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Characterization, Expression, and Immunohistochemical Localization of 3β-Hydroxysteroid Dehydrogenase/Δ5-Δ4 Isomerase in Human Skin
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Medical Adrenalectomy with Aminoglutethimide
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Steroid Profiling by Gas Chromatography–Mass Spectrometry and High Performance Liquid Chromatography–Mass Spectrometry for Adrenal Diseases
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Responses to Pure Antiestrogens (ICI 164384, ICI182780) in Estrogen‐Sensitive and‐Resistant Experimental and Clinical Breast Cancera
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3β-Hydroxysteroid Dehydrogenase Is a Possible Pharmacological Target in the Treatment of Castration-Resistant Prostate Cancer
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Complete Response of Metastatic Androgen Receptor–Positive Breast Cancer to Bicalutamide: Case Report and Review of the Literature
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The androgen metabolite 5α-androstane-3β,17β-diol (3βAdiol) induces breast cancer growth via estrogen receptor: implications for aromatase inhibitor resistance
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The backdoor pathway to dihydrotestosterone
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Gonadotropin hormone-releasing hormone analogues: a new therapeutic approach for prostatic carcinoma.
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Increased androgen receptor activity and cell proliferation in aromatase inhibitor-resistant breast carcinoma
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Abiraterone acetate, exemestane or the combination in postmenopausal patients with estrogen receptor-positive metastatic breast cancer
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Characterization of Corticotropin Receptors in Human Adrenocortical Cells*
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A-ring modified steroidal azoles retaining similar potent and slowly reversible CYP17A1 inhibition as abiraterone
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“Unfortunately, ketoconazole is a weak CYP17A1 inhibitor (Ki ∼130 nM) [96], and it strongly inhibits the important drug-metabolizing enzyme CYP3A4, thus limiting its clinical use.”
Background
Feedback control of luteinizing hormone and follicle-stimulating hormone secretion by testosterone and estradiol in men: physiologic and clinical implications
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Greasing the Wheels of the Cancer Machine: The Role of Lipid Metabolism in Cancer
Snaebjornsson, M. T., Janaki-Raman, S., & Schulze, A. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2019.11.010 · Cited by 1,097 · see citing works
Metal complexes in cancer therapy – an update from drug design perspective
Ndagi, U., Mhlongo, N. N., & Soliman, M. E. S. (2017) · Drug Design Development and Therapy · doi:10.2147/dddt.s119488 · Cited by 939 · see citing works
Hormonal Therapy for Prostate Cancer
Desai, K. B., McManus, J. M., & Sharifi, N. (2021) · Endocrine Reviews · doi:10.1210/endrev/bnab002 · Cited by 461 · see citing works
The Metabolic Phenotype of Prostate Cancer
Eidelman, E. R., Twum-Ampofo, J. K., Ansari, J., & Siddiqui, M. M. (2017) · Frontiers in Oncology · doi:10.3389/fonc.2017.00131 · Cited by 219 · see citing works
Intracrine androgen biosynthesis, metabolism and action revisited
Schiffer, L., Arlt, W., & Storbeck, K.-H. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.08.016 · Cited by 217 · see citing works
“, 2010), numerous studies have shown that CRPC is dependent on the intracrine conversion of circulating androgen precursors of adrenal origin to active androgens reviewed in (Capper et al., 2016; Luu-The et al., 2008; Pretorius et al., 2017; Sharifi and Auchus, 2012).”
Metabolic alterations in urine extracellular vesicles are associated to prostate cancer pathogenesis and progression
Clos‐Garcia, M., Loizaga‐Iriarte, A., Zúñiga-García, P., Sánchez‐Mosquera, P., Cortázar, A. R., González, E., Torrano, V., Alonso, C., Pérez-Cormenzana, M., Ugalde‐Olano, A., et al. (2018) · Journal of Extracellular Vesicles · doi:10.1080/20013078.2018.1470442 · Cited by 164 · see citing works
Estrogen and progesterone signalling in the normal breast and its implications for cancer development
Hilton, H. N., Clarke, C. L., & Graham, J. D. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.08.011 · Cited by 146 · see citing works
Peptide Conjugates with Small Molecules Designed to Enhance Efficacy and Safety
He, R., Finan, B., Mayer, J. P., & DiMarchi, R. D. (2019) · Molecules · doi:10.3390/molecules24101855 · Cited by 110 · see citing works
Sex Differences in Lung Cancer
May, L., Shows, K. H., Nana-Sinkam, P. S., Li, H. Y., & Landry, J. W. (2023) · Cancers · doi:10.3390/cancers15123111 · Cited by 106 · see citing works
Peptide-Drug Conjugates: A New Hope for Cancer Management
Chavda, V. P., Solanki, H. K., Davidson, M., Apostolopoulos, V., & Bojarska, J. (2022) · Molecules · doi:10.3390/molecules27217232 · Cited by 98 · see citing works
New inhibitor targeting Acyl-CoA synthetase 4 reduces breast and prostate tumor growth, therapeutic resistance and steroidogenesis
Castillo, A. F., Orlando, U. D., Maloberti, P. M., Prada, J. G., Dattilo, M. A., Solano, A. R., Bigi, M. M., Medrano, M. A. R., Torres, M. T., Indo, S., et al. (2020) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-020-03679-5 · Cited by 86 · see citing works
Long non-coding RNAs (lncRNAs) signaling in cancer chemoresistance: From prediction to druggability
Eptaminitaki, G. C., Stellas, D., Bonavida, B., & Baritaki, S. (2022) · Drug Resistance Updates · doi:10.1016/j.drup.2022.100866 · Cited by 77 · see citing works
Calycosin inhibits the in vitro and in vivo growth of breast cancer cells through WDR7-7-GPR30 Signaling
Tian, J., Wang, Y., Zhang, X., Ren, Q., Li, R., Huang, Y., Lu, H., & Chen, J. (2017) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-017-0625-y · Cited by 76 · see citing works
Small molecule drug conjugates (SMDCs): an emerging strategy for anticancer drug design and discovery
Patel, T. K., Adhikari, N., Amin, S. A., Biswas, S., Jha, T., & Ghosh, B. (2021) · New Journal of Chemistry · doi:10.1039/d0nj04134c · Cited by 68 · see citing works
Genome-wide crosstalk between steroid receptors in breast and prostate cancers
Paakinaho, V., & Palvimo, J. J. (2021) · Endocrine Related Cancer · doi:10.1530/erc-21-0038 · Cited by 55 · see citing works
Peroxisome Proliferator-Activated Receptors (PPAR)γ Agonists as Master Modulators of Tumor Tissue
Heudobler, D., Rechenmacher, M., Lüke, F., Vogelhuber, M., Pukrop, T., Herr, W., Ghibelli, L., Gerner, C., & Reichle, A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19113540 · Cited by 50 · see citing works
Efficient substrate screening and inhibitor testing of human CYP4Z1 using permeabilized recombinant fission yeast
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Additional file 2 of Expression profiles and functional prediction of long non-coding RNAs LINC01133, ZEB1-AS1 and ABHD11-AS1 in the luminal subtype of breast cancer
Mehrpour Layeghi, S., Arabpour, M., Shakoori, A., Naghizadeh, M. M., Mansoori, Y., Tavakkoly‐Bazzaz, J., & Esmaeili, R. (2021) · Figshare · doi:10.6084/m9.figshare.16456431
Additional file 3 of Expression profiles and functional prediction of long non-coding RNAs LINC01133, ZEB1-AS1 and ABHD11-AS1 in the luminal subtype of breast cancer
Mehrpour Layeghi, S., Arabpour, M., Shakoori, A., Naghizadeh, M. M., Mansoori, Y., Tavakkoly‐Bazzaz, J., & Esmaeili, R. (2021) · Figshare · doi:10.6084/m9.figshare.16456437
Additional file 1 of Testosterone upregulates glial cell line-derived neurotrophic factor (GDNF) and promotes neuroinflammation to enhance glioma cell survival and proliferation
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Additional file 4 of Expression profiles and functional prediction of long non-coding RNAs LINC01133, ZEB1-AS1 and ABHD11-AS1 in the luminal subtype of breast cancer
Mehrpour Layeghi, S., Arabpour, M., Shakoori, A., Naghizadeh, M. M., Mansoori, Y., Tavakkoly‐Bazzaz, J., & Esmaeili, R. (2021) · Figshare · doi:10.6084/m9.figshare.16456443
Additional file 2 of Testosterone upregulates glial cell line-derived neurotrophic factor (GDNF) and promotes neuroinflammation to enhance glioma cell survival and proliferation
Kanwore, K., Kanwore, K., Guo, X., Xia, Y., Zhou, H., Zhang, L., Adzika, G. K., Joseph, A.-A., Abiola, A. A., Peipei, M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.24310008
Additional file 1 of Expression profiles and functional prediction of long non-coding RNAs LINC01133, ZEB1-AS1 and ABHD11-AS1 in the luminal subtype of breast cancer
Mehrpour Layeghi, S., Arabpour, M., Shakoori, A., Naghizadeh, M. M., Mansoori, Y., Tavakkoly‐Bazzaz, J., & Esmaeili, R. (2021) · Figshare · doi:10.6084/m9.figshare.16456425
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Prostate Cancer Development, Progression, and Therapy
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BindingDB Entry 50009366: Design and Characterization of the First Selective and Potent Mechanism-Based Inhibitor of Cytochrome P450 4Z1.
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Authors: Capper, C. P., Rae, J. M., & Auchus, R. J.
Affiliations: University of Michigan (US)
Corresponding author: Auchus, Richard J.
ORCID: Capper, Cameron P.
Rae, James M.
Auchus, Richard J.
Venue: Hormones and Cancer
Publisher: Springer Science and Business Media LLC
Published: 2016-03-11
Volume: 7
Issue: 3
Pages: 149-164
ISSN: 1868-8497 (ISSN-L)
1868-8500
DOI: 10.1007/s12672-016-0259-0
PMC: PMC4860032
OpenAlex: W2294549982
Cited by: 89
References: 136
Citations by year: 2026: 8 · 2025: 7 · 2024: 4 · 2023: 7 · 2022: 10 · 2021: 20 · 2020: 6 · 2019: 7 · 2018: 8 · 2017: 10 · 2016: 2
FWCI: 1.56
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Hormones and Cancer (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (R01CA168899)
National Institute of General Medical Sciences (R01GM086596, R01GM099143)
Breast Cancer Research Foundation (N003173)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords: steroid hormone metabolism, steroidogenesis, breast cancer, prostate cancer, androgens, estrogen, endocrine therapy resistance, hormone-dependent tumors, metastatic disease
MeSH terms: Androgens, Animals, Antineoplastic Agents, Breast Neoplasms, Estrogens, Female, Gonads, Humans, Hypothalamo-Hypophyseal System, Male, Mutation, Pituitary-Adrenal System, Prostatic Neoplasms, Steroids, Signal Transduction, Receptors, Cytoplasmic and Nuclear, Molecular Targeted Therapy

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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

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Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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The metabolism, analysis, and targeting of steroid hormones in breast and prostate cancer

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

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Cites

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Record

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