Dame Roma Mitchell Cancer Research Laboratories and Adelaide Prostate Cancer Research Centre, University of Adelaide, SA 5000, Australia.
Nat Rev Urol. 2013 Aug;10(8):483-7. doi: 10.1038/nrurol.2013.126. Epub 2013 Jun 11.
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.
尽管有许多新的治疗方法用于治疗前列腺癌,但开发能够改善前列腺癌患者预后的药物仍然效率低下、成本高昂且进展缓慢。研究发现的临床转化面临的一个主要障碍是缺乏能够准确预测新药临床疗效的临床前模型,因此无法选择最适合临床试验的药物。一种在前列腺癌领域越来越受欢迎的方法是原代人组织的体外培养,这种方法可以保持肿瘤微环境的原始组织结构、激素反应性和细胞间信号传递处于动态和可操作的状态。体外培养系统在实验室环境中再现了人类前列腺癌的结构复杂性和异质性,因此成为当前基于细胞系和基于动物模型的重要辅助手段。当将其纳入临床前研究时,体外培养的组织可以对代表药物疗效的临床相关终点进行强有力的定量评估,还可以研究治疗耐药性和发现生物标志物。通过为前列腺癌发生提供新的临床相关见解,体外培养很可能会增强药物开发计划,并提高前列腺癌研究的转化“命中率”。