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Ex vivo culture of human prostate tissue and drug development

Abstract

Although an array of new therapeutics exist for prostate cancer, the development of agents that can improve outcomes for men with prostate cancer remains inefficient, costly, and frustratingly slow. A major impediment to the clinical translation of research findings is the lack of preclinical models that can accurately predict the clinical efficacy of new drugs and, therefore, enable the selection of agents that are most suitable for clinical trials. An approach that is gaining popularity in the prostate cancer community is ex vivo culture of primary human tissues, which retains the native tissue architecture, hormone responsiveness, and cell-to-cell signalling of the tumour microenvironment in a dynamic and manipulable state. Ex vivo culture systems recapitulate the structural complexity and heterogeneity of human prostate cancers in a laboratory setting, making them an important adjunct to current cell-line-based and animal-based models. When incorporated into preclinical studies, ex vivo cultured tissues enable robust quantitative evaluation of clinically relevant end points representing drug efficacy, investigation of therapy resistance, and biomarker discovery. By providing new clinically relevant insights into prostate carcinogenesis, it is likely that ex vivo culture will enhance drug development programmes and improve the translational 'hit rate' for prostate cancer research.

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Figure 1: Explant tissue culture methodologies.

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Acknowledgements

This work was supported by grants from the National Health and Medical Research Council of Australia (627185 and 1008349), Cancer Australia (627229), the Prostate Cancer Foundation of Australia (NDDA2711), the Royal Adelaide Hospital Research Committee, the Dorothy and James Cleo Thompson Foundation, National Institute of Health (R01 CA116777-05, R01 CA099996-09, and R01 ES016675-11). The Adelaide Prostate Cancer Centre is supported by an establishment grant from the Prostate Cancer Foundation of Australia (2011/0452). M. M. Centenera holds a Young Investigator Award from the Prostate Cancer Foundation of Australia (YI0412).

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M. M. Centenera and L. M. Butler researched, wrote, discussed, and edited the article. G. V. Raj, K. E. Knudsen, and W. D. Tilley contributed towards discussions of contents, edited, and reviewed the manuscript before submission.

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Correspondence to Lisa M. Butler.

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Centenera, M., Raj, G., Knudsen, K. et al. Ex vivo culture of human prostate tissue and drug development. Nat Rev Urol 10, 483–487 (2013). https://doi.org/10.1038/nrurol.2013.126

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