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Study on drug sensitivity and clinical application of tumor organoid-based colorectal cancer models
Yiwang Hu1, Junchang Zhu1, Yinjie Zheng1
1Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Nanbaixiang Campus Wenzhou 325000, Zhejiang, China.
Objectives:
To establish and validate a patient-derived organoid (PDO) model of colorectal cancer (CRC) for drug sensitivity testing and assess its correlation with clinical treatment outcomes.
Methods:
Tumor tissues were collected from 16 CRC patients undergoing surgery. PDOs were successfully generated from 9 cases and exposed to five chemotherapeutic agents (5-FU, oxaliplatin, irinotecan, raltitrexed, trifluridine) and one targeted therapy (cetuximab). IC50 values (half-maximal inhibitory concentration) and inhibition rates were determined and compared with patients' clinical responses.
Results:
PDOs displayed heterogeneity in drug sensitivity. RAS-mutant organoids were consistently resistant to cetuximab, whereas RAS wild-type organoids showed variable responses. In most cases, PDO drug responses correlated with clinical treatment outcomes, suggesting that the PDO model can accurately reflect individual therapeutic sensitivity.
Conclusions:
CRC PDOs can be efficiently established and serve as reliable in vitro models for predicting responses to chemotherapy and targeted therapies. This approach may guide personalized treatment strategies and improve clinical decision-making in CRC.
