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Establishment and large-scale validation of a three-dimensional tumor model on an array chip for anticancer drug
Rong-Rong Xiao1, Lei Jin2, Nan Xie2
1R&D Department, Beijing Daxiang Biotech Co., Ltd., Beijing, China.
Abstract:
Two-dimensional (2D) tumor model has always poorly predicted drug response of animal model due to the lack of recapitulation of tumor microenvironment. Establishing a biomimetic, controllable, and cost-effective three-dimensional (3D) model and large-scale validation of its in vivo predictivity has shown promise in bridging the gap between the 2D tumor model and animal model. Here, we established a matrigel-based 3D micro-tumor model on an array chip for large-scale anticancer drug evaluation. Compared with the 2D tumor model, the 3D tumor model on the chip showed spheroid morphology, slower proliferation kinetics, and comparable reproducibility. Next, the results of the chemotherapeutic evaluation from 18 drugs against 27 cancer cell lines showed 17.6% of drug resistance on the 3D tumor model. Moreover, the evaluation results of targeted drugs showed expected sensitivity and higher specificity on the 3D tumor model compared with the 2D model. Finally, the evaluation results on the 3D tumor model were more consistent with the in vivo cell-derived xenograft model, and excluded 95% false-positive results from the 2D model. Overall, the matrigel-based 3D micro-tumor model on the array chip provides a promising tool to accelerate anticancer drug discovery.
Insights
A novel three-dimensional (3D) micro-tumor model on a chip accurately predicts anticancer drug response, outperforming traditional 2D models and improving drug discovery efficiency.
Area of Science:
- Oncology
- Biomedical Engineering
- Drug Discovery
Background:
- Traditional 2D tumor models poorly predict drug response due to lacking tumor microenvironment.
- Bridging the gap between 2D models and animal models requires better predictive tools.
- Three-dimensional (3D) models offer a more biomimetic approach to cancer research.
Purpose of the Study:
- To establish a cost-effective, controllable 3D micro-tumor model on an array chip.
- To validate the *in vivo* predictivity of this 3D model for anticancer drug evaluation.
- To compare the performance of the 3D model against traditional 2D models and *in vivo* xenografts.
Main Methods:
- Development of a matrigel-based 3D micro-tumor model on an array chip.
- Large-scale evaluation of chemotherapeutic and targeted drugs against 27 cancer cell lines.
- Comparison of drug response data from 3D model, 2D model, and *in vivo* cell-derived xenograft models.
Main Results:
- The 3D tumor model exhibited spheroid morphology, slower proliferation, and comparable reproducibility to 2D models.
- Drug resistance was identified in 17.6% of cases using the 3D model.
- Targeted drugs showed improved sensitivity and specificity on the 3D model compared to the 2D model.
- The 3D model's results closely aligned with *in vivo* xenograft models, filtering out 95% of false positives from 2D models.
Conclusions:
- The matrigel-based 3D micro-tumor model on an array chip is a promising tool for anticancer drug discovery.
- This 3D model enhances the accuracy of drug response prediction compared to 2D models.
- The model accelerates the identification of effective anticancer therapies by improving *in vivo* predictivity.
