Androgenic effects of 11-oxyandrogens in castration-resistant prostate cancer
Bibliographic record
Abstract
BACKGROUND: Adrenal-derived 11-oxygenated androgens (11-oxyandrogens) emerged as potential key contributors to prostate cancer (PCa) progression by activating the androgen receptor (AR). This study investigates their clinical and mechanistic role in metastatic castration-resistant prostate cancer (mCRPC) patients initiating AR pathway inhibitors (ARPI). METHODS: In a pilot study of 35 mCRPC patients initiating ARPI, serum steroids were quantified via mass spectrometry and correlated with survival. Functional assays assessed the proliferative effects of 11-oxyandrogens on CRPC cells and their inhibition by enzalutamide, supported by transcriptomic and proteomic profiling. RESULTS: 11-ketotestosterone (11KT) and its hydroxylated derivative, 11-hydroxytestosterone (11OHT) are the predominant potent androgens, accounting for 81% of circulating androgens. Higher baseline levels of 11KT, 11OHT, the abundant precursor 11β-hydroxyandrostenedione (11OHA4), and the downstream metabolite 11-hydroxyandrosterone (11OHAST) are linked to prolonged progression-free survival (PFS) (HR: 0.56–0.69; P < 0.05), suggesting an enhanced treatment response. 11KT and 11OHT promoted AR-driven proliferation of CRPC cells and gene expression, which was reversed by AR antagonism, suggesting they are primarily AR-mediated. Additionally, 11-oxyandrogens display distinct effects, including the activation of AR-independent pathways. CONCLUSIONS: 11-oxyandrogens are potent AR activators in mCRPC, with evidence suggesting they may exert distinct biological effects compared to canonical androgens. Their association with longer PFS and improved response to ARPI may reflect a more hormonally active tumor environment, potentially indicative of tumors with higher AR dependency and responsiveness to therapy. Their profiling may help predict ARPI response, warranting further investigation.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".