Theranostics 2018; 8(19):5259-5275. doi:10.7150/thno.29098 This issue


Chemoresistance of Cancer Cells: Requirements of Tumor Microenvironment-mimicking In Vitro Models in Anti-Cancer Drug Development

Yeonho Jo1,2, Nakwon Choi2,3, Kyobum Kim4, Hyung-Jun Koo5, Jonghoon Choi1✉, Hong Nam Kim2,3✉

1. School of Integrative Engineering, Chung-Ang University, Seoul 06974, Republic of Korea
2. Center for BioMicrosystems, Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea
3. Division of Bio-Medical Science & Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea
4. Division of Bioengineering, Incheon National University, Incheon, Republic of Korea
5. Department of Chemical and Biomolecular Engineering, Seoul National University of Science and Technology, Seoul, Republic of Korea

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license ( See for full terms and conditions.
Jo Y, Choi N, Kim K, Koo HJ, Choi J, Kim HN. Chemoresistance of Cancer Cells: Requirements of Tumor Microenvironment-mimicking In Vitro Models in Anti-Cancer Drug Development. Theranostics 2018; 8(19):5259-5275. doi:10.7150/thno.29098. Available from

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Graphic abstract

For decades, scientists have been using two-dimensional cell culture platforms for high-throughput drug screening of anticancer drugs. Growing evidence indicates that the results of anti-cancer drug screening vary with the cell culture microenvironment, and this variation has been proposed as a reason for the high failure rate of clinical trials. Since the culture condition-dependent drug sensitivity of anti-cancer drugs may negatively impact the identification of clinically effective drug candidates, more reliable in vitro cancer platforms are urgently needed. In this review article, we provide an overview of how cell culture conditions can alter drug efficacy and highlight the importance of developing more reliable cancer drug testing platforms for use in the drug discovery process. The environmental factors that can alter drug delivery and efficacy are reviewed. Based on these observations of chemoresistant tumor physiology, we summarize the recent advances in the fabrication of in vitro cancer models and the model-dependent cytotoxicity of anti-cancer drugs, with a particular focus on engineered environmental factors in these platforms. It is believed that more physiologically relevant cancer models can revolutionize the drug discovery process.

Keywords: chemoresistance, tumor microenvironment, cancer cell, biomimetic, efficacy