Prostate Cancer Progression to Androgen Independent Disease: The Role of the Wnt/β-Catenin Pathway
Bibliographic record
Abstract
The development and progression of prostate cancer (CaP) is largely dependent on the dysregulation of the androgen/androgen receptor (AR) signaling pathway; though, the mechanism of CaP progression remains elusive. Initial treatments for CaP included prostatectomy or radiation to destroy cancerous cells (Feldman & Feldman, 2001). However, these treatments were not curative and more often than not there were recurrences and metastases of the cancer. Mainstay treatments that target the androgen/AR pathway through anti-androgen and androgen ablation therapies have been promising; yet again, these therapies seem to fail as the tumor progresses. This suggests that the androgen/AR dependence of CaP cells vary over time such that alterations in androgen availability, AR sensitivity and receptor promiscuity fuel a more aggressive CaP. Approximately 80-90% of CaPs are originally androgen dependent (AD) at diagnosis (Niu et al, 2010). Androgens stimulate the proliferation and inhibit the apoptosis of cells, thus implicating that CaP cells require a certain level of androgens to maintain their proliferation and survival (Feldman & Feldman, 2001). This is primarily the reason why androgen ablation therapy is initially successful—it removes the stimulation these cells require for proliferation, ultimately causing the regression of the tumor. However, over time patients often fail androgen ablation therapy as the tumor becomes a more lethal androgen independent (AI) or castration resistant form. There is no effective therapy for AI-CaP. The prostate requires androgenic steroids for its development and function. Testosterone is the main circulating androgen and is secreted from the testes as well as the adrenal glands (adrenal steroid conversion). Once in the blood stream, the majority of the testosterone binds to albumin and sex-hormone-binding globulin (SHBG) while a small fraction is freely dissolved within serum. Within the prostate, testosterone is converted to a derivative, dihydrotestosterone (DHT), by 5-alpha-reductase. DHT is a more potent and active form of testosterone and has a greater affinity for the AR relative to testosterone. Testosterone and DHT bind to the AR and causes its nuclear localization, transcriptional activation and its interaction with co-regulators/co-activators to mediate AR-directed gene transcription (Nui et al, 2010). The AR is required for the development of prostate carcinogenesis from early prostate intraepithelial neoplasia (PIN) to organ-confined or locally invasive primary tumors
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 teacher head, 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".