ReviewChemico-biological interactions2015
The DHEA-sulfate depot following P450c17 inhibition supports the case for AKR1C3 inhibition in high risk localized and advanced castration resistant prostate cancer.
Review in Chemico-biological interactions, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 59 citations in OpenAlex.
- Novel aldo-keto reductase 1C3 inhibitor affects androgen metabolism but not ovarian function in healthy women: a phase 1 study.European journal of endocrinology · 2023Trial
- Circulating and Intratumoral Adrenal Androgens Correlate with Response to Abiraterone in Men with Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Association of Tissue Abiraterone Levels andClinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Testicular vs adrenal sources of hydroxy-androgens in prostate cancer.Endocrine-related cancer · 2017Trial
- A Phase II Trial of Abiraterone Combined with Dutasteride for Men with Metastatic Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Trial
- Emerging therapies to overcome antiandrogen resistance and beyond in lethal prostate cancer.Journal of the National Cancer Center · 2026Review
- LX1 Dual Targets AR Variants and AKR1C3 in Advanced Prostate Cancer Therapy.Cancer research · 2024Article
- Characterization of prostate cancer adrenal metastases: dependence upon androgen receptor signaling and steroid hormones.Prostate cancer and prostatic diseases · 2023Article
- AKR1C3 Converts Castrate and Post-Abiraterone DHEA-S into Testosterone to Stimulate Growth of Prostate Cancer Cells via 5-Androstene-3β,17β-Diol.Cancer research communications · 2023Article
- Glucocorticoid receptor and androgen receptor-targeting therapy in patients with castration-resistant prostate cancer.Frontiers in oncology · 2022Article
- Drug resistance in metastatic castration-resistant prostate cancer: an update on the status quo.Cancer drug resistance (Alhambra, Calif.) · 2022Review
- Neoadjuvant hormonal therapy before radical prostatectomy in high-risk prostate cancer.Nature reviews. Urology · 2021Review
- Targeting backdoor androgen synthesis through AKR1C3 inhibition: A presurgical hormonal ablative neoadjuvant trial in high-risk localized prostate cancer.The Prostate · 2021Article
- Review
- Steroidogenesis in Peripheral and Transition Zones of Human Prostate Cancer Tissue.International journal of molecular sciences · 2021Article
- Dysregulated androgen synthesis and anti-androgen resistance in advanced prostate cancer.American journal of clinical and experimental urology · 2021Review
- Gene polymorphism-related differences in the outcomes of abiraterone for prostate cancer: a systematic overview.American journal of cancer research · 2021Review
- Steroid Sulfatase Stimulates Intracrine Androgen Synthesis and is a Therapeutic Target for Advanced Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- The role of adrenal derived androgens in castration resistant prostate cancer.The Journal of steroid biochemistry and molecular biology · 2020Review
- Intracrinology-revisited and prostate cancer.The Journal of steroid biochemistry and molecular biology · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 6 institutions in 1 country.
Funding
Abstract
Prostate cancer is the second leading cause of cancer death in the United States. Treatment of localized high-risk disease and de novo metastatic disease frequently leads to relapse. These metastatic castration resistant prostate cancers (mCRPC) claim a high mortality rate, despite the extended survival afforded by the growing armamentarium of androgen deprivation, radiation and immunotherapies. Here, we review two studies of neoadjuvant treatment of high-risk localized prostate cancer prior to prostatectomy, the total androgen pathway suppression (TAPS) trial and the neoadjuvant abiraterone acetate (AA) trial. These two trials assessed the efficacy of the non-specific P450c17 inhibitor, ketoconazole and the specific P450c17 inhibitor, AA, to inhibit tissue and serum androgen levels. Furthermore, a novel and validated stable isotope dilution liquid chromatography electrospray ionization selected reaction monitoring mass spectrometry assay was used to accurately quantify adrenal and gonadal androgens in circulation during the course of these trials. The adrenal androgens, Δ(4)-androstene-3,17-dione, dehydroepiandrosterone and dehydroepiandrosterone sulfate were significantly reduced in the patients receiving ketoconazole or AA compared to those who did not. However, in both trials, a significant amount of DHEA-S (∼20 μg/dL) persists and thus may serve as a depot for intratumoral conversion to the potent androgen receptor ligands, testosterone (T) and 5α-dihydrotestosterone (DHT). The final step in conversion of Δ(4)-androstene-3,17-dione and 5α-androstanedione to T and DHT, respectively, is catalyzed by AKR1C3. We therefore present the case that in the context of the DHEA-S depot, P450c17 and AKR1C3 inhibition may be an effective combinatorial treatment strategy.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.