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Organoids Increase the Predictive Value of Cancer Chemoprevention Studies for Outcome. | LitMetric

Organoids Increase the Predictive Value of Cancer Chemoprevention Studies for Outcome.

Front Oncol

Department of Urology, Northwestern University, Feinberg School of Medicine, Chicago, IL, United States.

Published: February 2019

AI Article Synopsis

  • Epidemiological and preclinical studies indicate that antioxidants, like selenium and vitamin E, may protect against prostate cancer linked to oxidative stress, but the SELECT trial showed no benefit from selenium and an increased risk from vitamin E.
  • The trial's outcomes challenge the effectiveness of traditional two-dimensional culture models used for testing chemoprevention agents, as these models don't accurately reflect real tumor biology.
  • The authors propose that three-dimensional organoid cultures may better simulate the native tissue environment and improve the predictive accuracy of future cancer prevention studies.

Article 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 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 studies for outcomes.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6391333PMC
http://dx.doi.org/10.3389/fonc.2019.00077DOI Listing

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