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Published on: June 14, 2018
Patient-derived organoids as a platform for drug screening in metastatic colorectal cancer
Xingfeng He1,2, Yan Jiang3, Long Zhang1,2
1Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China.
Abstract:
Introduction: Most advanced colorectal cancers are aggressive, and there is a lack of effective methods for selecting appropriate anticancer regimens. Patient-derived organoids (PDOs) have emerged as preclinical platforms for modeling clinical responses to cancer therapy. Methods: In this study, we successfully constructed a living biobank with 42 organoids derived from primary and metastatic lesions of metastatic colorectal cancer patients. Tumor tissue was obtained from patients undergoing surgical resection of the primary or metastatic lesion and then used to establish PDOs. Immunohistochemistry (IHC) and drug sensitivity assays were performed to analyze the properties of these organoids. Results: The mCRC organoids were successfully established with an 80% success rate. The PDOs maintained the genetic and phenotypic heterogeneity of their parental tumors. The IC50 values of5-fluorouracil (5-FU), oxaliplatin, and irinotecan (CPT11) were determined for mCRC organoids using drug sensitivity assays. The in vitro chemosensitivity data revealed the potential value of PDOs for clinical applications in predicting chemotherapy response and clinical outcomes in mCRC patients. Discussion: In summary, the PDO model is an effective platform for in vitro assessment of patient-specific drug sensitivity, which can guide personalized treatment decisions for patients with end-stage CRC.
Insights
Patient-derived organoids (PDOs) effectively model metastatic colorectal cancer (mCRC) and predict chemotherapy response. This biobank of 42 organoids guides personalized treatment decisions for advanced CRC patients.
Area of Science:
- Oncology
- Cancer Biology
- Translational Medicine
Background:
- Advanced colorectal cancers (CRC) are aggressive with limited treatment selection options.
- Patient-derived organoids (PDOs) show promise as preclinical models for predicting cancer therapy response.
- Developing reliable models is crucial for personalized medicine in metastatic CRC (mCRC).
Purpose of the Study:
- To establish a living biobank of organoids from metastatic colorectal cancer (mCRC) patients.
- To assess the utility of PDOs in modeling tumor heterogeneity and predicting drug sensitivity.
- To evaluate PDOs as a tool for guiding personalized chemotherapy regimens in mCRC.
Main Methods:
- Established 42 organoids from primary and metastatic lesions of mCRC patients.
- Utilized immunohistochemistry (IHC) and drug sensitivity assays on PDOs.
- Determined IC50 values for 5-fluorouracil (5-FU), oxaliplatin, and irinotecan (CPT11).
Main Results:
- Achieved an 80% success rate in establishing mCRC organoids.
- PDOs successfully recapitulated the genetic and phenotypic heterogeneity of parental tumors.
- In vitro chemosensitivity data correlated with potential clinical outcomes.
Conclusions:
- The PDO biobank is a valuable resource for studying mCRC.
- PDOs accurately reflect patient tumor characteristics and drug responses.
- This model can guide personalized treatment strategies for mCRC patients.
