Abstract
Epidemiological and preclinical data suggest that antioxidants are protective against prostate cancer whose pathogenesis has been linked to oxidative stress. However, the selenium and vitamin E Cancer Prevention Trial (SELECT), found no efficacy for selenium in reducing prostate cancer incidence while vitamin E was associated with an increased risk of the disease. These results have called in to question the models used in preclinical chemoprevention efficacy studies and their ability to predict in vivo outcomes. Chemoprevention agents have traditionally been tested on two dimensional monolayer cultures of cell lines derived from advanced prostate cancers. But as SELECT demonstrates, results from advanced disease models were not predictive of the outcome of a primary chemoprevention trial. Additionally, lack of cell-matrix interactions in two dimensional cultures results in loss of biochemical and mechanical cues relevant for native tissue architecture. We use recent findings in three dimensional organoid cultures that recapitulated the SELECT trial results to argue that the organoid model could increase the predictive value of in vitro studies for in vivo outcomes.
Highlights
Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous male malignancy in the United States
PCa growth and progression is driven by androgens making androgen deprivation therapy through surgical or medical castration, the standard treatment for advanced and metastatic PCa [8, 9]
Effects of the mean concentrations of the selenium and vitamin E Cancer Prevention Trial (SELECT) agents attained in the blood plasma of the SELECT participants was evaluated in prostate organoids derived from normal, premalignant, and malignant prostate epithelial cells [122]
Summary
Prostate cancer (PCa) is the most commonly diagnosed non-cutaneous male malignancy in the United States. For men with local or regional disease at diagnosis, radical prostatectomy, or radiation therapy are effective treatments with a 100% 5-year survival rate [2]. 20–40% radical prostatectomy and 30–50% radiation therapy patients will experience biochemical recurrence within 10 years [5,6,7]. PCa growth and progression is driven by androgens making androgen deprivation therapy through surgical or medical castration, the standard treatment for advanced and metastatic PCa [8, 9]. There is progression to castration resistant disease, whose treatments confer a median overall survival benefit of less than 5 months [10,11,12,13,14,15,16]. Given the drawbacks of screening, treatment associated morbidity and lack of effective treatments for advanced disease, preventing PCa is imperative
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