Institute of Molecular and Translational Medicine, Faculty of Medicine and Dentistry, Palacky University Olomouc, Hněvotínská 5, 779 00 Olomouc, Czech Republic; EATRIS Headquarters, Giovanni Migliaccio, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands.
Experimental Pharmacology Unit, Istituto Nazionale per lo Studio e la Cura dei Tumori Fondazioni Giovanni Pascale - IRCCS, 80131 Naples, Italy; EATRIS Headquarters, Giovanni Migliaccio, De Boelelaan 1118, 1081 HZ Amsterdam, The Netherlands.
Drug Discov Today. 2015 Jul;20(7):848-55. doi: 10.1016/j.drudis.2015.04.004. Epub 2015 Apr 20.
The alarming rate of failure of clinical trials is a major hurdle in cancer therapy that partly results from the inadequate use of in vitro tumor models for the screening of promising hits and leads in preclinical studies. 2D cultures of cancer cell lines that are primarily used for drug screening do not adequately recapitulate tumor microenvironment (TME) complexities compared with 3D cancer cell cultures and tumor-derived primary cell cultures. In this review, we focus on the potential use of in vitro tumor models that reproduce in vivo tumor complexities for effective drug selection in the preclinical stages of drug development.
临床试验失败率令人震惊,这是癌症治疗的主要障碍,部分原因是在临床前研究中,体外肿瘤模型在筛选有前途的命中靶点和先导化合物方面的应用不足。用于药物筛选的主要癌症细胞系 2D 培养物与 3D 癌症细胞培养物和肿瘤源性原代细胞培养物相比,不能充分重现肿瘤微环境(TME)的复杂性。在这篇综述中,我们重点介绍了用于药物开发的临床前阶段有效药物选择的体外肿瘤模型,这些模型可以复制体内肿瘤的复杂性。