Highly Mimetic Ex Vivo Lung-Cancer Spheroid-Based Physiological Model for Clinical Precision Therapeutics

Area of Science:

• Oncology
• Biotechnology
• Regenerative Medicine

Background:

• Lung cancer poses a significant global health challenge, necessitating advanced research tools for effective prevention and treatment.
• Understanding tumor biology is crucial for developing patient-specific models to investigate cancer metastasis and therapeutic strategies.

Purpose of the Study:

• To biofabricate patient-specific ex vivo lung cancer models for precise investigation of tumor behavior and treatment response.
• To create a model that replicates native tumor biophysicochemical properties and oxygen gradients for precision medicine applications.

Main Methods:

• Development of biofabricated lung tumors using patient-derived tumor spheroids, endothelial cells, and decellularized lung extracellular matrix.
• Characterization of the model for radial oxygen gradients and biophysicochemical behaviors mimicking native tumors.
• Validation of the model's predictive capability through co-clinical trials assessing responses to chemotherapy and targeted therapy.

Main Results:

• The developed lung cancer spheroid model accurately replicated patient responses to chemotherapeutics and targeted therapy with 85% accuracy, 86.7% sensitivity, and 80% specificity.
• RNA sequencing confirmed that gene expression within the spheroids closely mirrored that of the patient's primary tumor.
• The model successfully maintained key characteristics of native tumors, including radial oxygen gradients.

Conclusions:

• The biofabricated lung cancer spheroid model serves as a powerful ex vivo predictive tool for personalized cancer therapy.
• This model has the potential to significantly improve the quality of clinical care by enabling more accurate treatment selection.
• Further application of this model can accelerate the development of novel lung cancer treatment strategies.