Related Experiment Video
Updated: Jul 16, 2025
Establishment of Zebrafish Patient-Derived Xenografts from Pancreatic Cancer for Chemosensitivity Testing
Published on: May 12, 2023
Real time ex vivo chemosensitivity assay for pancreatic adenocarcinoma
Dae Won Kim1, Francisca Beato1, Youngchul Kim2
1Department of Gastrointestinal Oncology, Moffitt Cancer Center, Tampa, FL 33612, USA.
Background:
Patient-derived organoids (PDOs) and xenografts (PDXs) have been extensively studied for drug-screening. However, their usage is limited due to lengthy establishment time, high engraftment failure rates and different tumor microenvironment from original tumors. To overcome the limitations, we developed real time-live tissue sensitivity assay (RT-LTSA) using fresh tumor samples.
Methods:
Tissue slices from resected pancreatic cancer samples were placed in 96-well plates, and the slices were treated with chemotherapeutic agents. The correlation between the chemo-sensitivity of tissue slices and each patient's clinical outcome was analyzed.
Results:
The viability and tumor microenvironment of the tissue slices are well-preserved over 5 days. The drug sensitivity assay results are available within 5 days after tissue collection. While all 4 patients who received RT-LTSA sensitive adjuvant regimens did not develop recurrence, 7 of 8 patients who received resistant adjuvant regimens developed recurrence. We observed significantly improved disease-free survival in the patients who received RT-LTSA sensitive adjuvant regimens (median: not reached versus 10.6 months, P = 0.02) compared with the patient who received resistant regimens. A significant negative correlation between RT-LTSA value and relapse-free survival was observed (Somer's D: -0.58; P = 0.016).
Conclusions:
RT-LTSA which maintains the tumor microenvironment and architecture as found in patients may reflect clinical outcome and could be used as a personalized strategy for pancreatic adenocarcinoma. Further, studies are warranted to verify the findings.
Insights
A new real-time live tissue sensitivity assay (RT-LTSA) for pancreatic cancer offers rapid drug screening. This method preserves tumor microenvironment, showing promising correlations with patient outcomes and personalized treatment strategies.
Area of Science:
- Oncology
- Translational Research
- Drug Discovery
Background:
- Patient-derived organoids (PDOs) and xenografts (PDXs) are used for drug screening but have limitations including long establishment times, high failure rates, and altered tumor microenvironments.
- These limitations hinder their clinical applicability for personalized cancer therapy.
Purpose of the Study:
- To develop a rapid drug sensitivity assay using fresh tumor samples that overcomes the limitations of PDOs and PDXs.
- To establish a real-time live tissue sensitivity assay (RT-LTSA) for pancreatic cancer that preserves the native tumor microenvironment and architecture.
Main Methods:
- Fresh pancreatic cancer tissue slices were obtained from resected samples and placed in 96-well plates.
- Tissue slices were treated with various chemotherapeutic agents to assess drug sensitivity.
- The correlation between the drug sensitivity results from RT-LTSA and individual patient clinical outcomes was analyzed.
Main Results:
- The RT-LTSA preserved the viability and tumor microenvironment of tissue slices for up to 5 days.
- Drug sensitivity results were available within 5 days of tissue collection, enabling timely treatment decisions.
- Patients receiving RT-LTSA-guided sensitive adjuvant regimens showed no recurrence, while 7 of 8 receiving resistant regimens recurred (P=0.02).
- A significant negative correlation was observed between RT-LTSA results and relapse-free survival (Somer's D: -0.58; P=0.016).
Conclusions:
- RT-LTSA effectively maintains the tumor microenvironment and architecture, accurately reflecting patient clinical outcomes.
- This assay holds potential as a personalized strategy for treating pancreatic adenocarcinoma.
- Further studies are required to validate these promising findings in larger cohorts.
