Application of colorectal cancer organoid-on-a-chip in the tumor microenvironment, cancer drug development and drug screening

Colorectal cancer is now the third leading cause of cancer-related death in women and men in US, primarily due to the high incidence of cancer metastasis and chemotherapeutic treatment inefficiency. Access to high-quality, physiologically relevant in vitro cancer models are therefore essential for evaluating the efficacy of compounds, identifying drug resistance mechanisms, and exploring therapeutic targets. 

The development of advanced in vitro models has been critical in improving cancer drug screening. Widely used traditional 2-D cell cultures have many limitations, such as the absence of tumor heterogeneity, lack of tumor microenvironment complexity, and lack of 3-D architecture. In contrast, cancer organoid models more closely mimic the structure of tumors in vivo, including cell-cell and cell-matrix interactions, and allow for the creation of drug-resistance niches. Here, we propose that the most promising approachable models are cancer organoid-on-a-chip models, which combine 3-D cancer organoids with microfluidic devices. These systems provide the tumor microenvironment and organ-level physiological responses, providing a more accurate and controlled environment for drug testing. The fluidic microenvironment allows for dynamic, real-time drug exposure to tumor cells, more accurately reflecting physiological drug exposure in human patients. 

To support the development of cancer organoid-on-a-chip models, ATCC provides over 300 next-generation cancer models, including 78 expanded colorectal cancer organoids, developed by the Human Cancer Models Initiative (HCMI) for academic and commercial use. These models are manufactured, characterized, and validated at ATCC and provide essential tools for aiding cancer research and drug discovery. 

In this study, we used the colorectal cancer organoids from our HCMI collection to demonstrate that colorectal cancer organoid-on-a-chip models can be used for drug sensitivity testing by delivering compounds to in vitro cancer models under conditions that replicate real physiological drug exposure. Our data suggest that this novel tumoroid-on-a-chip microfluidic system successfully mimics the tumor microenvironment and the complex organ-level physiological and pharmacological responses.