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Updated: Jul 31, 2025
High-sensitivity Detection of Micrometastases Generated by GFP Lentivirus-transduced Organoids Cultured from a Patient-derived Colon Tumor
Published on: June 14, 2018
Precision medicine applied to metastatic colorectal cancer using tumor-derived organoids and in-vitro sensitivity
Lars Henrik Jensen1,2,3, Silvia Regina Rogatto4,5,6, Jan Lindebjerg4,7
1Department of Oncology, University Hospital of Southern Denmark, Lillebaelt Hospital, Beriderbakken 4, Vejle, 7100, Denmark. lars.henrik.jensen@rsyd.dk.
Background:
Patients with colorectal metastatic disease have a poor prognosis, limited therapeutic options, and frequent development of resistance. Strategies based on tumor-derived organoids are a powerful tool to assess drug sensitivity at an individual level and to suggest new treatment options or re-challenge. Here, we evaluated the method's feasibility and clinical outcome as applied to patients with no satisfactory treatment options.
Methods:
In this phase 2, single-center, open-label, non-comparative study (ClinicalTrials.gov, register NCT03251612), we enrolled 90 patients with metastatic colorectal cancer following progression on or after standard therapy. Participants were 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-2, adequate organ function, and metastasis available for biopsy. Biopsies from the metastatic site were cultured using organoids model. Sensitivity testing was performed with a panel of drugs with proven activity in phase II or III trials. At the discretion of the investigator considering toxicity, the drug with the highest relative activity was offered. The primary endpoint was the proportion of patients alive without disease progression at two months per local assessment.
Results:
Biopsies available from 82 to 90 patients were processed for cell culture, of which 44 successfully generated organoids with at least one treatment suggested. The precision cohort of 34 patients started treatment and the primary endpoint, progression-free survival (PFS) at two months was met in 17 patients (50%, 95% CI 32-68), exceeding the pre-defined level (14 of 45; 31%). The median PFS was 67 days (95% CI 51-108), and the median overall survival was 189 days (95% CI 103-277).
Conclusions:
Patient-derived organoids and in-vitro sensitivity testing were feasible in a cohort of metastatic colorectal cancer. The primary endpoint was met, as half of the patients were without progression at two months. Cancer patients may benefit from functional testing using tumor-derived organoids.
Trial Registration:
ClinicalTrials.gov, register NCT03251612.
Insights
Tumor organoids enable personalized drug testing for metastatic colorectal cancer patients. This approach showed feasibility and met its primary endpoint, with half of patients progression-free at two months.
Area of Science:
- Oncology
- Translational Medicine
- Drug Discovery
Background:
- Metastatic colorectal cancer (mCRC) presents poor prognosis and limited treatment options.
- Tumor-derived organoids offer a platform for personalized drug sensitivity assessment.
- This study investigated the feasibility and clinical utility of organoids in mCRC patients with limited therapeutic choices.
Purpose of the Study:
- To evaluate the feasibility of using patient-derived organoids for drug sensitivity testing in mCRC.
- To assess the clinical outcome of patients treated based on organoid sensitivity data.
- To determine if organoid-based testing can identify effective treatment strategies for refractory mCRC.
Main Methods:
- A phase 2, single-center study enrolled 90 mCRC patients progressing on standard therapy.
- Metastatic biopsies were used to generate patient-derived organoids.
- Organoids underwent drug sensitivity testing with agents active in phase II/III trials.
- Investigators selected treatments based on highest relative organoid activity.
Main Results:
- Organoids were successfully generated from 44 out of 82 processed biopsies.
- The primary endpoint (progression-free survival at two months) was met by 50% (17/34) of patients in the precision cohort.
- Median progression-free survival was 67 days, and median overall survival was 189 days.
Conclusions:
- Patient-derived organoids are feasible for drug sensitivity testing in mCRC.
- Organoid-based treatment selection achieved the primary endpoint, with 50% of patients progression-free at two months.
- Functional testing using tumor organoids shows potential clinical benefit for cancer patients.
