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Cancer-on-a-chip for Drug Screening
I-Chi Lee1,2
1Graduate Institute of Biomedical Engineering, Chang Gung University, Taoyuan, Taiwan.
Abstract:
The oncology pharmaceutical research spent a shocking amount of money on target validation and drug optimization in preclinical models because many oncology drugs fail during clinical trial phase III. One of the most important reasons for oncology drug failures in clinical trials may due to the poor predictive tool of existing preclinical models. Therefore, in cancer research and personalized medicine field, it is critical to improve the effectiveness of preclinical predictions of the drug response of patients to therapies and to reduce costly failures in clinical trials. Three dimensional (3D) tumor models combine micro-manufacturing technologies mimic critical physiologic parameters present in vivo, including complex multicellular architecture with multicellular arrangement and extracellular matrix deposition, packed 3D structures with cell-cell interactions, such as tight junctions, barriers to mass transport of drugs, nutrients and other factors, which are similar to in vivo tumor tissues. These systems provide a solution to mimic the physiological environment for improving predictive accuracy in oncology drug discovery. This review gives an overview of the innovations, development and limitations of different types of tumor-like construction techniques such as self-assemble spheroid formation, spheroids formation by micro-manufacturing technologies, micro-dissected tumor tissues and tumor organoid. Combination of 3D tumor-like construction and microfluidic techniques to achieve tumor on a chip for in vitro tumor environment modeling and drug screening were all included. Eventually, developmental directions and technical challenges in the research field are also discussed. We believe tumor on chip models have provided better sufficient clinical predictive power and will bridge the gap between proof-of-concept studies and a wider implementation within the oncology drug development for pathophysiological applications.
Insights
Three dimensional (3D) tumor models and tumor-on-a-chip systems improve preclinical drug testing accuracy. These advanced models better predict patient response to oncology therapies, reducing costly clinical trial failures.
Area of Science:
- Oncology
- Biotechnology
- Drug Discovery
Background:
- High oncology drug failure rates in clinical trials are linked to inadequate preclinical predictive models.
- Existing preclinical models fail to replicate the complex in vivo tumor microenvironment.
Purpose of the Study:
- To review innovations and limitations of 3D tumor models for improved drug response prediction.
- To highlight the potential of tumor-on-a-chip systems in oncology drug development.
Main Methods:
- Overview of self-assembly spheroids, micro-manufactured spheroids, micro-dissected tissues, and organoids.
- Discussion of 3D tumor models combined with microfluidics for "tumor on a chip" applications.
Main Results:
- 3D tumor models recapitulate in vivo physiological parameters like multicellular architecture and mass transport barriers.
- "Tumor on a chip" systems offer enhanced in vitro modeling of tumor environments for drug screening.
Conclusions:
- Advanced 3D tumor models and "tumor on a chip" systems show promise for increasing clinical predictive power.
- These models can bridge the gap between early research and clinical application in oncology drug development.
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