Patient-derived tumor spheroid-induced angiogenesis preclinical platform for exploring therapeutic vulnerabilities in...

Area of Science:

• Oncology
• Biomedical Engineering
• Translational Medicine

Background:

• Current preclinical cancer models often fail to accurately replicate the complex tumor microenvironment.
• There is a need for advanced models that support patient-treatment decisions and clarify tumor biology.
• Understanding tumor-driven angiogenesis is critical for developing effective cancer therapies.

Purpose of the Study:

• To develop and validate an advanced, non-animal preclinical cancer model.
• To reconstruct the tumor microenvironment focusing on patient-derived tumor spheroids (PDTS) and angiogenesis.
• To assess the efficacy of targeted therapies within this novel model.

Main Methods:

• Development of a microfluidic chip system incorporating patient-derived tumor spheroids (PDTS).
• Reconstruction of the tumor microenvironment to mimic tumor spheroid-driven angiogenesis.
• Application of a vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor (ramucirumab) to assess therapeutic response.
• Testing of drug combinations including HER2 and angiogenesis inhibitors.

Main Results:

• The microfluidic chip system successfully recapitulated patient-specific tumor conditions and angiogenic responses.
• Vascularized PDTS demonstrated significant angiogenesis and tumor proliferation on the chip.
• Ramucirumab effectively inhibited angiogenesis and impeded tumor invasion.
• The model allowed for the investigation of distinct responses to various drug combinations.

Conclusions:

• This innovative preclinical model accurately reflects tumor microenvironment complexities, including angiogenesis.
• The model provides a robust platform for evaluating targeted therapies and drug combinations.
• This approach holds potential for advancing precision medicine by integrating tumor microenvironment data.