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Updated: Oct 3, 2025
Author Spotlight: Creating Human Vascularized Micro-Tumors as Models for Translational Cancer Research
Published on: September 15, 2023
Vascularized Tumor Spheroid-on-a-Chip Model Verifies Synergistic Vasoprotective and Chemotherapeutic Effects
Zhiwei Hu1,2, Yuanxiong Cao1,2, Edgar A Galan1,2
1Institute of Biopharmaceutical and Health Engineering, Shenzhen International Graduate School (SIGS), Tsinghua University, Shenzhen 518055, China.
Abstract:
Prolyl hydroxylases (PHD) inhibitors have been observed to improve drug distribution in mice tumors via blood vessel normalization, increasing the effectiveness of chemotherapy. These effects are yet to be demonstrated in human cell models. Tumor spheroids are three-dimensional cell clusters that have demonstrated great potential in drug evaluation for personalized medicine. Here, we used a perfusable vascularized tumor spheroid-on-a-chip to simulate the tumor microenvironment in vivo and demonstrated that the PHD inhibitor dimethylallyl glycine prevents the degradation of normal blood vessels while enhancing the efficacy of the anticancer drugs paclitaxel and cisplatin in human esophageal carcinoma (Eca-109) spheroids. Our results point to the potential of this model to evaluate anticancer drugs under more physiologically relevant conditions.
Insights
Prolyl hydroxylase inhibitors normalize tumor blood vessels, enhancing chemotherapy. This study validates this effect in human esophageal cancer spheroids using a novel 3D tumor-on-a-chip model.
Area of Science:
- Oncology
- Vascular Biology
- Drug Discovery
Background:
- Prolyl hydroxylase (PHD) inhibitors have shown promise in normalizing tumor vasculature and improving chemotherapy efficacy in preclinical models.
- Translating these findings to human cell models is crucial for advancing cancer treatment.
- Tumor spheroids offer a 3D platform for evaluating drug responses in a more physiologically relevant context.
Purpose of the Study:
- To investigate the efficacy of a PHD inhibitor in normalizing blood vessels within a human esophageal carcinoma spheroid model.
- To assess the combined effect of a PHD inhibitor and standard chemotherapeutic agents (paclitaxel, cisplatin) on tumor spheroid growth and drug delivery.
- To validate a perfusable vascularized tumor spheroid-on-a-chip model for evaluating anticancer drug efficacy.
Main Methods:
- Development and utilization of a perfusable vascularized tumor spheroid-on-a-chip system.
- Treatment of human esophageal carcinoma (Eca-109) spheroids with a PHD inhibitor (dimethylallyl glycine) alone and in combination with paclitaxel and cisplatin.
- Assessment of blood vessel integrity and anticancer drug efficacy within the spheroids.
Main Results:
- The PHD inhibitor dimethylallyl glycine prevented the degradation of normal blood vessels in the tumor spheroids.
- Combined treatment with the PHD inhibitor and anticancer drugs significantly enhanced drug efficacy compared to monotherapy.
- The tumor-on-a-chip model successfully simulated key aspects of the in vivo tumor microenvironment.
Conclusions:
- The study demonstrates the potential of PHD inhibitors to improve anticancer drug delivery and efficacy in human esophageal cancer models.
- The vascularized tumor spheroid-on-a-chip platform provides a valuable tool for preclinical evaluation of cancer therapeutics under physiologically relevant conditions.
- These findings support the further development of PHD inhibitors as a strategy to enhance chemotherapy in clinical settings.
