Longitudinal Circulating Tumor Cell Collection, Culture, and Characterization in Pancreatic Adenocarcinomas

Area of Science:

• Oncology
• Molecular Biology
• Genomics

Background:

• Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer with poor treatment outcomes due to chemoresistance.
• Liquid biopsies using circulating tumor cells (CTCs) offer a non-invasive method to study tumor evolution and resistance mechanisms.

Purpose of the Study:

• To longitudinally collect, culture, and characterize CTCs from PDAC patients.
• To elucidate molecular mechanisms of chemoresistance and identify patient-specific gene expression profiles.

Main Methods:

• Collected blood samples from 10 PDAC patients across treatment stages, establishing 16 CTC cultures.
• Performed differential gene expression, pathway dysregulation, and protein-protein interaction analyses.
• Conducted longitudinal comparisons in five patients to track dynamic molecular changes.

Main Results:

• CTC cultures showed activation of pathways like TNFα/NF-kB, hedgehog signaling, and EMT.
• Longitudinal analysis identified dynamic changes in PI3K/Akt/mTOR and TGF-β pathways, indicating chemoresistance.
• Protein-protein interaction analysis highlighted the immune system's role in PDAC progression and therapy response.

Conclusions:

• Demonstrated the feasibility of longitudinal CTC capture and analysis in PDAC patients.
• Provided insights into molecular drivers of chemoresistance and potential for personalized medicine.
• Highlighted CTC profiling as a promising approach for informing PDAC treatment strategies.