Patient‐Derived Organoids from Colorectal Cancer with Paired Liver Metastasis Reveal Tumor Heterogeneity and Predict Response to Chemotherapy

There is no effective method to predict chemotherapy response and postoperative prognosis of colorectal cancer liver metastasis (CRLM) patients. Patient‐derived organoid (PDO) has become an important preclinical model. Herein, a living biobank with 50 CRLM organoids derived from primary tumors and paired liver metastatic lesions is successfully constructed. CRLM PDOs from the multiomics levels (histopathology, genome, transcriptome and single‐cell sequencing) are comprehensively analyzed and confirmed that this organoid platform for CRLM could capture intra‐ and interpatient heterogeneity. The chemosensitivity data in vitro reveal the potential value of clinical application for PDOs to predict chemotherapy response (FOLFOX or FOLFIRI) and clinical prognosis of CRLM patients. Taken together, CRLM PDOs can be utilized to deliver a potential application for personalized medicine. A living biobank of patient‐derived organoid (PDO) is derived from primary colorectal cancer and paired liver metastatic lesions, which captures intra‐ and interpatient molecular fingerprint heterogeneity. PDO chemosensitivity measured in vitro may be used as a predictive tool for clinical chemotherapeutic efficacy, and guide the formulation of precise treatment strategies for colorectal cancer patients with liver metastases.