Related Experiment Video
Updated: Aug 15, 2026
High-sensitivity Detection of Micrometastases Generated by GFP Lentivirus-transduced Organoids Cultured from a Patient-derived Colon Tumor
Published on: June 14, 2018
Implementing patient derived organoids in functional precision medicine for patients with advanced colorectal cancer
Jérôme Cartry1, Sabrina Bedja2, Alice Boilève2
1Inserm U-1279, Gustave Roussy, Université Paris-Saclay, Villejuif, F-94805, France. jerome.cartry@gustaveroussy.fr.
Background:
Patient Derived Organoids (PDOs) emerged as the best technology to develop ex vivo tumor avatars. Whether drug testing on PDOs to identify efficient therapies will bring clinical utility by improving patient survival remains unclear. To test this hypothesis in the frame of clinical trials, PDO technology faces three main challenges to be implemented in routine clinical practices: i) generating PDOs with a limited amount of tumor material; ii) testing a wide panel of anti-cancer drugs; and iii) obtaining results within a time frame compatible with patient disease management. We aimed to address these challenges in a prospective study in patients with colorectal cancer (CRC).
Methods:
Fresh surgical or core needle biopsies were obtained from patients with CRC. PDOs were established and challenged with a panel of 25 FDA-approved anti-cancer drugs (chemotherapies and targeted therapies) to establish a scoring method ('chemogram') identifying in vitro responders. The results were analyzed at the scale of the cohort and individual patients when the follow-up data were available.
Results:
A total of 25 PDOs were successfully established, harboring 94% concordance with the genomic profile of the tumor they were derived from. The take-on rate for PDOs derived from core needle biopsies was 61.5%. A chemogram was obtained with a 6-week median turnaround time (range, 4-10 weeks). At least one hit (mean 6.16) was identified for 92% of the PDOs. The number of hits was inversely correlated to disease metastatic dissemination and the number of lines of treatment the patient received. The chemograms were compared to clinical data obtained from 8 patients and proved to be predictive of their response with 75% sensitivity and specificity.
Conclusions:
We show that PDO-based drug tests can be achieved in the frame of routine clinical practice. The chemogram could provide clinicians with a decision-making tool to tailor patient treatment. Thus, PDO-based functional precision oncology should now be tested in interventional trials assessing its clinical utility for patients who do not harbor activable genomic alterations or have developed resistance to standard of care treatments.
Insights
Patient-derived organoids (PDOs) show promise for predicting colorectal cancer treatment response. This functional precision oncology approach, using a drug sensitivity scoring method called a chemogram, can guide clinical decisions and improve patient outcomes.
Area of Science:
- Oncology
- Genomics
- Drug Discovery
Background:
- Patient-derived organoids (PDOs) are a key technology for creating ex vivo tumor avatars.
- The clinical utility of PDO drug testing for improving patient survival remains under investigation.
- Implementing PDO technology in routine clinical practice faces challenges including limited tumor material, broad drug screening, and timely results.
Purpose of the Study:
- To assess the feasibility of PDO-based drug sensitivity testing in routine clinical practice for colorectal cancer (CRC) patients.
- To address challenges in PDO generation, drug panel testing, and result turnaround time.
- To evaluate the predictive value of PDO drug response for clinical outcomes.
Main Methods:
- Prospective study involving CRC patients.
- Establishment of PDOs from surgical or core needle biopsies.
- Drug sensitivity testing using 25 FDA-approved anti-cancer drugs and a 'chemogram' scoring method.
Main Results:
- Successfully established 25 PDOs with 94% genomic concordance.
- Achieved a 61.5% PDO take-on rate from core needle biopsies.
- Median turnaround time for chemogram generation was 6 weeks.
- Identified at least one effective drug ('hit') for 92% of PDOs.
- Chemograms predicted patient response with 75% sensitivity and specificity in 8 patients.
Conclusions:
- PDO-based drug testing is feasible within routine clinical practice.
- The chemogram can serve as a decision-making tool for tailoring patient treatments.
- Further interventional trials are needed to confirm the clinical utility of PDO-based functional precision oncology, especially for patients with limited treatment options.
More Related Videos
04:49Creating Matched In vivo/In vitro Patient-Derived Model Pairs of PDX and PDX-Derived Organoids for Cancer Pharmacology Research
Published on: May 5, 2021
07:31Author Spotlight: Establishment of Pancreatic Cancer-Derived Tumor Organoids and Fibroblasts From Fresh Tissue
Published on: May 26, 2023
