Cited by 107Prostate Cancer Treatment and ResearchProstate Cancer Diagnosis and TreatmentHormonal and reproductive studies

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Castration-recurrent prostate cancer is not androgen-independent.

Mohler, James L.·2008·Advances in experimental medicine and biology

DOI 10.1007/978-0-387-69080-3_21

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Abstract

An American man is diagnosed with prostate cancer (PC) every 3 min and dies from the disease every 17 min. Although androgen receptor (AR) expression is diminished following androgen deprivation therapy (ADT) that induces clinical remission in most patients, castration-recurrent PC expresses levels of AR protein similar to those found in androgen-stimulated PC and benign prostate. This observation suggests that the AR may be as important for growth regulation in castration-recurrent PC, as it is in androgen-stimulated PC and benign hyperplasia. Neither ligand-independence, point mutations, glutamine and/or glycine repeat expansion nor amplification have explained AR activation in most cases of castration-recurrent PC. Castration-recurrent PC tissue has levels of testosterone (T) similar to androgen-stimulated benign prostate and levels of dihydrotestosterone (DHT), the most active androgen for AR activation that are approximately 10% of androgen-stimulated benign prostate. These levels of tissue androgens appear capable of activating the AR since prostate-specific antigen (PSA), the classic androgen-regulated gene, is expressed at similar tissue levels in castration-recurrent and androgen-stimulated PC. These startling findings suggest a paradigm shift; PC that recurs during ADT is not androgen-independent.

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Authors: Mohler, J. L.
Affiliations: University of North Carolina at Chapel Hill (US)
Corresponding author: Mohler, James L.
ORCID: Mohler, James L.
Venue: Advances in experimental medicine and biology
Publisher: Springer New York
Published: 2008
Volume: 617
Pages: 223-234
ISSN: 0065-2598 (ISSN-L)
DOI: 10.1007/978-0-387-69080-3_21
OpenAlex: W202356157
Cited by: 106
References: 57
Citations by year: 2025: 1 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 4 · 2018: 4 · 2017: 4 · 2016: 9 · 2015: 9 · 2014: 9 · 2013: 15 · 2012: 8
FWCI: 62.53
Type: book chapter
Language: en
Open access: closed
Locations: Advances in experimental medicine and biology (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
Health Sciences › Medicine › Urology › Prostate Cancer Diagnosis and Treatment
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
Keywords: castration-resistant prostate cancer, recurrent prostate cancer, androgen receptor, androgen-independent growth, androgen deprivation therapy, dihydrotestosterone, testosterone, prostate-specific antigen, androgen receptor activation, benign prostatic hyperplasia
MeSH terms: Androgens, Humans, Male, Neoplasm Recurrence, Local, Neoplasms, Hormone-Dependent, Orchiectomy, Prostatic Neoplasms, Receptors, Androgen

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Castration-recurrent prostate cancer is not androgen-independent.

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