Personalized Vascularized Tumor Organoid-on-a-Chip for Tumor Metastasis and Therapeutic Targeting Assessment

Area of Science:

• Biomedical Engineering
• Cancer Research
• Oncology

Background:

• Tumor organoids lack functional vasculature, limiting their physiological relevance for studying cancer.
• Existing vascularized organoid models fail to replicate the hierarchical microvasculature found in vivo.
• This gap hinders research on tumor progression and therapies targeting tumor vasculature.

Purpose of the Study:

• To develop an innovative vascularized patient-derived tumor organoids (PDTOs)-on-a-chip platform.
• To create a system with hierarchical, tumor-specific microvasculature for studying tumor-vascular dynamics.
• To evaluate the efficacy of anti-vascular therapies and understand tumor metastasis.

Main Methods:

• Development of a PDTOs-on-a-chip system with integrated microvasculature.
• Utilizing patient-derived tumor cells to establish organoids.
• Investigating tumor cell migration and angiogenesis using the developed platform.
• Analyzing the role of the Notch pathway in tumor cell migration and vessel formation.

Main Results:

• The PDTOs-on-a-chip platform successfully recapitulated hierarchical, tumor-specific microvasculature.
• Highly metastatic tumor cells were observed to induce vessel angiogenesis and migrate towards blood vessels.
• The Notch pathway was identified as a key mediator in tumor cell migration and angiogenesis.
• A correlation was found between PDTO angiogenic/migratory capacity and clinical metastatic outcomes.

Conclusions:

• The developed vascularized PDTOs-on-a-chip system offers a physiologically relevant platform for cancer research.
• This model can be used to study tumor-vascular interactions, metastasis, and anti-vascular drug efficacy.
• The platform provides insights into clinical metastatic potential and aids in personalized treatment strategy development.