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Published on: March 10, 2017
High-throughput screening (HTS) of anticancer drug efficacy on a micropillar/microwell chip platform
Dong Woo Lee1, Yeon-Sook Choi, Yun Jee Seo
1Central R & D Institute, Samsung Electro-mechanics Company, Ltd. , 314, Maetan 3-Dong, Yeongtong-Gu, Suwon-Si, 443-743 Gyeonggi-Do, Republic of Korea.
Abstract:
Contemporary cancer therapy refers to treatment based on genetic abnormalities found in patient's 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.
Insights
A new chip platform enables personalized cancer therapy by testing drug efficacy on patient tumor cells. This approach shows patient-specific drug responses, correlating with genetic data and improving treatment strategies.
Area of Science:
- Biotechnology
- Oncology
- Genomics
Background:
- Personalized gene-targeted cancer therapy faces challenges like tumor heterogeneity and limited patient samples.
- Current methods struggle with rapid drug efficacy testing on scarce primary cancer cells.
Purpose of the Study:
- To develop a novel micropillar/microwell chip platform for personalized cancer therapy.
- To generate in vitro drug efficacy data comparable to clinical and gene expression data.
Main Methods:
- Encapsulating primary cancer cells in hydrogel droplets on a micropillar/microwell chip.
- Testing the therapeutic efficacy of 24 anticancer drugs on cancer cell lines and patient-derived cells.
- Measuring drug dose responses and IC50 values.
Main Results:
- The chip platform successfully encapsulated cancer cells and generated drug efficacy data.
- Patient-derived brain cancer cells exhibited unique responses to 24 tested anticancer drugs.
- Drug efficacy showed correlation with oncogene overexpression (c-Met, FGFR1) and prior in vivo xenograft model results.
Conclusions:
- The developed chip platform is suitable for personalized gene-targeted cancer therapy.
- In vitro drug efficacy testing on the chip platform can predict patient-specific responses.
- This technology has the potential to improve clinical outcomes in cancer treatment.
