Abstract 858: Enzalutamide versus abiraterone as a radiosensitizer in hormone-sensitive prostate cancer cells
Bibliographic record
Abstract
Abstract Prostate cancer treatment is based on the estimated risk of recurrence in the U.S. Combined androgen deprivation therapy (ADT) with radiation therapy (XRT) is the standard of care for high-risk localized PCa. However, a large percentage of tumors are resistance to ADT due to continued AR signaling. Abiraterone (ABI), an androgen synthesis inhibitor, and Enzalutamide (ENZA), a potent AR antagonist, are new treatment options for metastatic castration resistance prostate cancer (mCRPC) patients. The aim of this study is to compare the efficacy of ENZA or ABI as a radiosensitizer in XRT therapy on PCa cells. Methods: The effect of ENZA or ABI alone or in combination with XRT was assessed on hormone-sensitive (LNCaP, PC3-AR-T877A) and insensitive (PC3, PC3-AR V7) PCa cells using cell viability (MTT) and also clonogenic assays in different scheduling regimens: A- drug 24 h before XRT, B-drug 2h before XRT, or C- XRT followed by 24h later drug. Results: We first determined the effect of ENZA or ABI on MTT assays in androgen-dependent (AD) and androgen-independent (AI) PCa cell lines. The results of MTT assay showed that ENZA inhibited the growth of the four different cell lines, LNCaP, PC3-T877A, PC3 and PC3 AR-V7 with IC50 values of 20, 22, 50, and 45μmol/L, respectively, after 24 hours of treatment. The same effect was observed on ABI treated cell lines. Radiosensitivity was not significantly increased in AD and AI PCa cell lines by ABI (DEF=1.00, in all cases) while there was a supra-additive dose enhancement factor (DEF= 1.75±0.08) for hormone-sensitive cells treated with ENZA (Table 1). Conclusion: Our data indicates that ENZA acts as a much stronger radiosensitizer compared to ABI through different probable mechanisms of radiosensitivity. Table 1. Dose Enhancement Factors calculations by scheduling ProtocolABCENZAABIENZAABIENZAABIADLNCaP1.35±0.021.05±0.011.75±0.081.001.30±0.051.00PC3-AR T877A1.30±0.031.001.65±0.011.001.35±0.061.05±0.02AIPC31.001.001.001.001.001.00PC3-AR V71.001.001.001.001.001.00 Citation Format: Maryam Ghashghaei, Thierry Muanza, Moulay Alaoui-Jamali, Miltiadis Paliouras, Mohammad Tamim Niazi. Enzalutamide versus abiraterone as a radiosensitizer in hormone-sensitive prostate cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 858.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".