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

Authors
Jo, YeonhoChoi, NakwonKim, KyobumKoo, Hyung-JunChoi, JonghoonKim, Hong Nam
Issue Date
2018-10
Publisher
IVYSPRING INT PUBL
Citation
THERANOSTICS, v.8, no.19, pp.5259 - 5275
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
INTERSTITIAL FLUID PRESSURE; ON-A-CHIP; PANCREATIC-CANCER; SOLID TUMORS; EXTRACELLULAR-MATRIX; GROWTH-FACTORS; MULTIDRUG-RESISTANCE; COLORECTAL-CANCER; INITIATING CELLS; ECM INTERACTIONS; INTERSTITIAL FLUID PRESSURE; ON-A-CHIP; PANCREATIC-CANCER; SOLID TUMORS; EXTRACELLULAR-MATRIX; GROWTH-FACTORS; MULTIDRUG-RESISTANCE; COLORECTAL-CANCER; INITIATING CELLS; ECM INTERACTIONS; chemoresistance; tumor microenvironment; cancer cell; biomimetic; efficacy
ISSN
1838-7640
URI
https://pubs.kist.re.kr/handle/201004/120877
DOI
10.7150/thno.29098
Appears in Collections:
KIST Article > 2018
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