High-Throughput Screening (HTS) of Anticancer Drug Efficacy on a Micropillar/Microwell Chip Platform

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• 作者：Dong Woo Lee ; Yeon-Sook Choi ; Yun Jee Seo ; Moo-Yeal Lee ; Sang Youl Jeon ; Bosung Ku ; Sangjin Kim ; Sang Hyun Yi ; Do-Hyun Nam
• 刊名：Analytical Chemistry
• 出版年：2014
• 出版时间：January 7, 2014
• 年：2014
• 卷：86
• 期：1
• 页码：535-542
• 全文大小：493K
• ISSN：1520-6882

文摘

Contemporary cancer therapy refers to treatment based on genetic abnormalities found in patient鈥檚 tumor. However, this approach is faced with numerous challenges, including tumor heterogeneity and molecular evolution, insufficient tumor samples available along with genetic information linking to clinical outcomes, lack of therapeutic drugs containing pharmacogenomic information, and technical limitations of rapid drug efficacy tests with insufficient quantities of primary cancer cells from patients. To address these problems and improve clinical outcomes of current personalized gene-targeted cancer therapy, we have developed a micropillar/microwell chip platform, which is ideally suited for encapsulating primary cancer cells in nanoscale spots of hydrogels on the chip, generating efficacy data with various drugs, eventually allowing for a comparison of the in vitro data obtained from the chip with clinical data as well as gene expression data. As a proof of concept in this study, we have encapsulated a U251 brain cancer cell line and three primary brain cancer cells from patients (448T, 464T, and 775T) in 30 nL droplets of alginate and then tested the therapeutic efficacy of 24 anticancer drugs by measuring their dose responses. As a result, the IC₅₀ values of 24 anticancer drugs obtained from the brain cancer cells clearly showed patient cell-specific efficacy, some of which were well-correlated with their oncogene overexpression (c-Met and FGFR1) as well as the in vivo previous results of the mouse xenograft model with the three primary brain cancer cells.