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Organoid Sensitivity Correlates with Therapeutic Response in Patients with Pancreatic Cancer
Joseph E Grossman1,2, Lakshmi Muthuswamy1,2, Ling Huang1,2
1BIDMC Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Purpose:
Pancreatic ductal adenocarcinoma (PDAC) remains a significant health issue. For most patients, there are no options for targeted therapy, and existing treatments are limited by toxicity. The HOPE trial (Harnessing Organoids for PErsonalized Therapy) was a pilot feasibility trial aiming to prospectively generate patient-derived organoids (PDO) from patients with PDAC and test their drug sensitivity and correlation with clinical outcomes.
Experimental Design:
PDOs were established from a heterogeneous population of patients with PDAC including both basal and classical PDAC subtypes.
Results:
A method for classifying PDOs as sensitive or resistant to chemotherapy regimens was developed to predict the clinical outcome of patients. Drug sensitivity testing on PDOs correlated with clinical responses to treatment in individual patients.
Conclusions:
These data support the investigation of PDOs to guide treatment in prospective interventional trials in PDAC.
Insights
Patient-derived organoids (PDOs) from pancreatic cancer (PDAC) can predict treatment response. This feasibility study shows PDO drug sensitivity correlates with patient outcomes, supporting their use in future clinical trials.
Area of Science:
- Oncology
- Translational Research
- Cancer Therapeutics
Background:
- Pancreatic ductal adenocarcinoma (PDAC) presents a major health challenge with limited targeted therapy options and toxic conventional treatments.
- Developing effective therapeutic strategies for PDAC is crucial due to poor patient outcomes.
Purpose of the Study:
- To prospectively generate patient-derived organoids (PDOs) from PDAC patients.
- To assess the drug sensitivity of PDOs.
- To correlate PDO drug sensitivity with clinical outcomes in PDAC patients.
Main Methods:
- Patient-derived organoids (PDOs) were established from a diverse group of PDAC patients, encompassing both basal and classical subtypes.
- A classification system was developed to categorize PDOs as sensitive or resistant to specific chemotherapy regimens.
- Drug sensitivity assays were performed on PDOs to evaluate their response to various treatments.
Main Results:
- The developed method successfully classified PDOs based on their sensitivity or resistance to chemotherapy.
- Drug sensitivity testing using PDOs demonstrated a correlation with the clinical treatment responses observed in individual PDAC patients.
- The study established a link between in vitro PDO drug response and in vivo patient outcomes.
Conclusions:
- Patient-derived organoids show promise as a predictive tool for chemotherapy response in pancreatic cancer.
- The findings support the utility of PDOs in guiding personalized treatment strategies for PDAC.
- Further investigation of PDOs in prospective interventional trials for PDAC is warranted.
