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Challenges & Opportunities Toward Enabling Phenotypic Screening of Complex & Three-Dimensional Cell Models

Horman, Shane, Hogan, Christopher, Karlo, Reyes and Antczak, Christophe (2015) Challenges & Opportunities Toward Enabling Phenotypic Screening of Complex & Three-Dimensional Cell Models. Future Medicinal Chemistry, 7 (4). pp. 513-525.

Abstract

Increasingly, organotypic cellular platforms are being recognized as useful tools for early stage drug discovery initiatives. Novel complex and three-dimensional (3D) cell culture techniques have been integrated into contemporary phenotypic screening practices and miniaturized to accommodate the vast chemical libraries used by biotechnology and pharmaceutical industries. This review offers an industry-centric perspective on emerging 3D cell culture technologies currently employed by large pharmaceutical companies. The benefits of using complex cellular platforms over conventional two-dimensional (2D) systems are described as well as the challenges and opportunities for incorporating these types of multidimensional platforms into high-throughput screening (HTS). We particularly highlight the colony formation and spheroid multicellular platforms, as well as the need for novel chemical sensors to noninvasively quantitate 3D structures in real time. Further, we contend that the use of more focused chemical and genomics libraries will enable the screening of complex cell models derived from primary and induced pluripotent stem (iPS) cells, to expand the patient relevancy of high content drug discovery efforts. Finally, we offer outlooks on several emerging technologies that show great potential for future integration of complex cell systems into contemporary drug screening.

Item Type: Article
Date Deposited: 13 Oct 2015 13:12
Last Modified: 13 Oct 2015 13:12
URI: https://oak.novartis.com/id/eprint/22839

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