Related Experiment Video
Updated: Dec 20, 2025
Isolation and Characterization of Patient-derived Pancreatic Ductal Adenocarcinoma Organoid Models
Published on: January 14, 2020
Patient-derived pancreatic tumour organoids identify therapeutic responses to oncolytic adenoviruses
Giulia Raimondi1, Ana Mato-Berciano1, Silvia Pascual-Sabater1
1Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Background:
Pancreatic patient-derived organoids (PDOs) are a well-established model for studying pancreatic ductal adenocarcinoma (PDAC) carcinogenesis and are potential predictors of clinical responses to chemotherapy. Oncolytic virotherapy is envisioned as a novel treatment modality for pancreatic cancer, and candidate viruses are being tested in clinical trials. Here, we explore the feasibility of using PDOs as a screening platform for the oncolytic adenovirus (OA) response.
Methods:
Organoids were established from healthy pancreas and PDAC tissues and assessed for infectivity, oncoselectivity, and patient-dependent sensitivity to OA. Antitumour effects were studied in vivo in organoid xenografts. Further evaluation of oncolytic responses was conducted in organoids derived from orthotopic models or metastastic tissues.
Findings:
Oncolytic adenoviruses display good selectivity, with replication only in organoids derived from PDAC tumours. Furthermore, responses of PDOs to a set of OAs reveal individual differences in cytotoxicity as well as in synergism with standard chemotherapy. Adenoviral cytotoxicity in PDOs is predictive of antitumour efficacy in a subcutaneous xenograft setting. Organoids from orthotopic tumours and metastases in nude mice mirror the viral preference of PDOs, indicating that PDO sensitivity to OAs could be informative about responses in both primary tumours and metastatic foci.
Interpretation:
Our data imply that pancreatic PDOs can serve as predictive tools for screening for sensitivity to OA.
Insights
Pancreatic patient-derived organoids (PDOs) effectively predict oncolytic adenovirus (OA) treatment response in pancreatic cancer. This model shows individual differences and potential for personalized therapy screening.
Area of Science:
- Oncology
- Virology
- Biotechnology
Background:
- Pancreatic patient-derived organoids (PDOs) model pancreatic ductal adenocarcinoma (PDAC) and predict chemotherapy response.
- Oncolytic virotherapy is an emerging treatment for pancreatic cancer, with viruses undergoing clinical trials.
- This study investigates PDOs as a platform for screening oncolytic adenovirus (OA) efficacy.
Purpose of the Study:
- To assess the feasibility of using PDOs for screening oncolytic adenovirus (OA) response in pancreatic cancer.
- To evaluate the infectivity, oncoselectivity, and patient-dependent sensitivity of PDOs to OAs.
- To determine if PDO response to OAs predicts in vivo antitumour efficacy.
Main Methods:
- Organoids were derived from healthy pancreas and PDAC tissues.
- Infectivity, oncoselectivity, and OA sensitivity were assessed in PDOs.
- Antitumour effects were evaluated in organoid xenografts and organoids from orthotopic/metastatic models.
Main Results:
- Oncolytic adenoviruses selectively replicated in PDAC-derived organoids.
- PDOs exhibited patient-specific cytotoxicity and synergism with chemotherapy when treated with OAs.
- Adenoviral cytotoxicity in PDOs correlated with antitumour efficacy in xenografts.
- Organoids from orthotopic and metastatic models mirrored PDO viral preference.
Conclusions:
- Pancreatic PDOs serve as predictive tools for screening OA sensitivity.
- PDOs can inform about responses in both primary tumors and metastatic foci.
- This model supports personalized oncolytic virotherapy strategies for pancreatic cancer.
