Abstract LB-176: The human androgen receptor regulates DNA damage response (DDR) in prostate cancer
Bibliographic record
Abstract
Abstract Clinical studies have shown the improved benefit of combining androgen deprivation therapy (ADT) with radiotherapy, indicating a potential interaction between the androgen signalling and DNA damage response (DDR) pathways in PCa. We have explored the underlying basis of this interaction by interrogating the mechanism of androgen regulation of the DDR in men with PCa, both untreated and treated with an androgen inhibitor. We show that androgen receptor (AR) signalling regulates the DDR and promotes DDR foci formation leading to ATM activation in PCa. Our data showing that AR regulates DDR provides an explanation for the improved outcome of combined ADT and radiotherapy. Thus, our work identifies the rationale for targeting both the AR and DDR pathways simultaneously to improve therapy outcome in advanced or high risk prostate cancer. Citation Format: Mohammad Asim, Heather Zecchini, Firas Tarish, Charlie Massie, Ajoeb Baridi, Anne Warren, Wanfeng Zhao, Leigh-Anne McDuffus, Patrice Mascalchi, Greg Shaw, Harveer Dev, Karan Wadhwa, Paul Wijnhoven, Josep Forment, Scott Lyons, Andy Lynch, Cormac O’Neill, Vincent Zecchini, Paul Rennie, Aria Baniahmad, Simon Tavare, Ian Mills, Niklas Schulz, Yaron Galanty, Thomas Helleday, David Neal. The human androgen receptor regulates DNA damage response (DDR) in prostate cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-176.
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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 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.022 | 0.006 |
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".