Pancreatic Cancer Patient-derived Organoids Can Predict Response to Neoadjuvant Chemotherapy

Area of Science:

• Oncology
• Translational Research
• Biomarker Development

Background:

• Patient-derived organoids (PDOs) show promise as biomarkers for therapy response and personalized medicine in pancreatic cancer.
• Existing research has explored PDOs, but a comprehensive biobank with diverse patient populations is needed.

Purpose of the Study:

• To evaluate the predictive capability of PDOs for neoadjuvant chemotherapy (NAT) response in pancreatic adenocarcinoma.
• To establish a large, diverse organoid biobank for pancreatic cancer research.
• To assess the feasibility of rapid drug screening using PDOs.

Main Methods:

• Collected 136 samples from 117 pancreatic cancer patients (2017-2021) including diverse demographics.
• Established PDO cultures from surgical resections and fine needle aspiration/biopsy.
• Performed molecular profiling and drug sensitivity testing on PDOs, including rapid screening.

Main Results:

• Successful PDO generation rates were 71% from post-NAT and 76% from chemotherapy-naive tissue.
• Pathological response to NAT correlated with PDO chemotherapy response, especially to oxaliplatin.
• Demonstrated rapid PDO drug screening, yielding data within 7 days of tissue resection.

Conclusions:

• A large single-institution organoid biobank, including ethnic minority samples, was established.
• Longitudinal PDO generation from pre- and post-chemotherapy samples allows dynamic sensitivity profiling.
• Rapid PDO screening can aid in stratifying pancreatic cancer patients to effective NAT regimens.