Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE.
Expert Opin Drug Discov. 2021 Aug;16(8):841-850. doi: 10.1080/17460441.2021.1912731. Epub 2021 Apr 26.
The high failure rate in drug discovery remains a costly and time-consuming challenge. Improving the odds of success in the early steps of drug development requires disease models with high biological relevance for biomarker discovery and drug development. The adoption of three-dimensional (3D) cell culture systems over traditional monolayers in cell-based assays is considered a promising step toward improving the success rate in drug discovery.
In this article, the author focuses on new technologies for 3D cell culture and their applications in cancer drug discovery. Besides the most common 3D cell-culture systems for tumor cells, the article emphasizes the need for 3D cell culture technologies that can mimic the complex tumor microenvironment and cancer stem cell niche.
There has been a rapid increase in 3D cell culture technologies in recent years in an effort to more closely mimic in vivo physiology. Each 3D cell culture system has its own strengths and weaknesses with regard to in vivo tumor growth and the tumor microenvironment. This requires careful consideration of which 3D cell culture system is chosen for drug discovery and should be based on factors like drug target and tumor origin.
药物发现的高失败率仍然是一个代价高昂且耗时的挑战。提高药物开发早期阶段成功的几率需要具有高生物学相关性的疾病模型,以便用于生物标志物发现和药物开发。与基于细胞的测定中的传统单层相比,采用三维(3D)细胞培养系统被认为是提高药物发现成功率的一个有前途的步骤。
本文作者重点介绍了 3D 细胞培养的新技术及其在癌症药物发现中的应用。除了最常见的用于肿瘤细胞的 3D 细胞培养系统外,本文还强调了需要能够模拟复杂肿瘤微环境和癌症干细胞生态位的 3D 细胞培养技术。
近年来,为了更紧密地模拟体内生理学,3D 细胞培养技术迅速增加。每个 3D 细胞培养系统在体内肿瘤生长和肿瘤微环境方面都有其自身的优势和劣势。这需要仔细考虑选择哪种 3D 细胞培养系统用于药物发现,并且应该基于药物靶点和肿瘤起源等因素。