Ex vivo culture of human prostate tissue and drug development

被引:115
作者
Centenera, Margaret M. [1 ,2 ]
Raj, Ganesh V. [3 ]
Knudsen, Karen E. [4 ]
Tilley, Wayne D. [1 ,2 ]
Butler, Lisa M. [1 ,2 ]
机构
[1] Univ Adelaide, Dame Roma Mitchell Canc Res Labs, Adelaide, SA 5000, Australia
[2] Univ Adelaide, Adelaide Prostate Canc Res Ctr, Adelaide, SA 5000, Australia
[3] UT Southwestern Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA
[4] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA
基金
英国医学研究理事会;
关键词
IN-VITRO; INCREASED SURVIVAL; CLINICAL-TRIALS; ORGAN-CULTURE; CANCER; GROWTH; BENIGN; HYPERPLASIA; MODEL; CARCINOGENESIS;
D O I
10.1038/nrurol.2013.126
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
100201 [内科学]; 100221 [泌尿外科学];
摘要
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.
引用
收藏
页码:483 / 487
页数:5
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