Real-time and regional analysis of the efficacy of anticancer drugs in a patient-derived intratumoral heterogeneous tumor microenvironment†

Abstract

Preclinical evaluation of anticancer drug efficacy utilizes 2D cell culture systems, tumoroids or experimental animal models, but it suffers from limitations such as inaccurate simulation of tumor microenvironments in living tumors, difficulty in regional analysis, and low throughput. Therefore, in this study, we developed a system named tumor-microenvironment-on-chip (TMoC) comprising a 3D dynamic tumor tissue culture system, which recreated diverse and heterogeneous cellular tumor microenvironments. In addition to the culture with a dynamic circulation, TMoC allowed users to perform real-time regional analysis, independently assessing the drug response from the normoxic area to the hypoxic area in a gradient manner. Through cell composition analysis and gene analysis, we proved that TMoC has a tumor environment with close resemblance to the original tumor environment. By comparing 15 drug testing results with animal experiments, we proved that TMoC is 93% consistent with the response results of animal experiments. In addition, we confirmed that either mouse- or patient-derived tumor cell lines can be cultured and tested in TMoC, indicating its immense potential for all aspects of preclinical drug evaluation.