Personalized drug screening in patient-derived organoids of biliary tract cancer and its clinical application

作者：Xiaoxue Ren, Mingle Huang, Weixiang Weng, Yubin Xie, Yifan Wu, Shenghua Zhu, Ying Zhang, Dongming Li, Jiaming Lai, Shunli Shen, Jie Lin, Ming Kuang, Xiaoxing Li, Jun Yu, Lixia Xu · 发表于：Cell Reports Medicine · 年份：2023 · DOI：10.1016/j.xcrm.2023.101277 · 被引用次数：52 · 研究领域：Cholangiocarcinoma and Gallbladder Cancer Studies、Hepatocellular Carcinoma Treatment and Prognosis、Cancer Genomics and Diagnostics

Patients with biliary tract cancer (BTC) show different responses to chemotherapy, and there is no effective way to predict chemotherapeutic response. We have generated 61 BTC patient-derived organoids (PDOs) from 82 tumors (74.4%) that show similar histological and genetic characteristics to the corresponding primary BTC tissues. BTC tumor tissues with enhanced stemness- and proliferation-related gene expression by RNA sequencing can more easily form organoids. As expected, BTC PDOs show different responses to the chemotherapies of gemcitabine, cisplatin, 5-fluoruracil, oxaliplatin, etc. The drug screening results in PDOs are further validated in PDO-based xenografts and confirmed in 92.3% (12/13) of BTC patients with actual clinical response. Moreover, we have identified gene expression signatures of BTC PDOs with different drug responses and established gene expression panels to predict chemotherapy response in BTC patients. In conclusion, BTC PDO is a promising precision medicine tool for anti-cancer therapy in BTC patients.