Pancreatic Cancer Organoids: Modeling Disease and Guiding Therapy

Area of Science:

• Oncology
• Biomedical Engineering
• Translational Medicine

Background:

• Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer with limited treatment options.
• Existing in vitro models fail to capture tumor complexity and stromal interactions crucial for chemoresistance.
• There is a critical need for reliable biomarkers and models for personalized medicine in PDAC.

Purpose of the Study:

• To provide a comprehensive review of patient-derived organoids (PDOs) in pancreatic cancer research.
• To highlight the fidelity, predictive value, and integration of tumor microenvironment (TME) components in PDO models.
• To discuss emerging technologies and future directions for PDO applications in PDAC.

Main Methods:

• Review of existing literature on PDAC patient-derived organoids (PDOs).
• Analysis of PDO genetic and phenotypic fidelity compared to primary tumors.
• Evaluation of PDO drug testing platforms and integration with TME components and advanced technologies.

Main Results:

• PDOs faithfully recapitulate the genetic features and intratumoral heterogeneity of primary PDAC.
• PDO drug sensitivity strongly correlates with in vivo efficacy, validating their predictive power.
• Innovative co-culture systems and integration with microphysiological systems enhance TME modeling.

Conclusions:

• PDOs are valuable tools for functional precision medicine in PDAC, enabling reliable drug response prediction.
• Integrating TME components and advanced technologies like AI can improve PDO models for drug discovery.
• Standardization and regulatory acceptance are key to fully realizing the potential of PDOs for PDAC patients.