Friend or foe? Deciphering androgen receptor action to improve bipolar androgen therapy for prostate cancer
Bibliographic record
Abstract
Inhibiting the activity of the androgen receptor (AR) is the cornerstone treatment for advanced prostate cancer. AR-targeted therapies are highly effective in slowing disease progression but are not curative. Failure of these therapies results in a disease state termed castration-resistant prostate cancer, which is associated with significant patient morbidity and mortality. In most cases, resistance to AR-targeted therapies arises due to alterations that reactivate the AR signalling axis. Interestingly, it has long been recognised that potent activation of AR with supraphysiological levels of androgens can suppress prostate cancer growth in both preclinical models and patients. This intriguing paradox, where both inhibition and activation of AR have anti-cancer effects, is now being harnessed clinically in the form of bipolar androgen therapy (BAT). This review describes mechanisms underlying the tumour-suppressive functions of AR in the context of potent androgenic stimulation and discusses how our maturing understanding of these processes is influencing the clinical deployment of BAT.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.005 | 0.002 |
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".