Patient-Derived Organoids Predict Chemoradiation Responses of Locally Advanced Rectal Cancer
Ye Yao, Xiaoya Xu, Lifeng Yang, Ji Zhu, Juefeng Wan, Lijun Shen, Fan Xia, Guoxiang Fu, Yun Deng, Mengxue Pan, Qiang Guo, Xiaoxue Gao, Yuanchuang Li, Xinxin Rao, Yi Zhou, Liping Liang, Yaqi Wang, Jing Zhang, Hui Zhang, Guichao Li, Lixing Zhang, Junjie Peng, Sanjun Cai, Chen Hu, Jianjun Gao, Hans Clevers, Zhen Zhang, Guoqiang Hua, Ye Yao, Xiaoya Xu, Lifeng Yang, Ji Zhu, Juefeng Wan, Lijun Shen, Fan Xia, Guoxiang Fu, Yun Deng, Mengxue Pan, Qiang Guo, Xiaoxue Gao, Yuanchuang Li, Xinxin Rao, Yi Zhou, Liping Liang, Yaqi Wang, Jing Zhang, Hui Zhang, Guichao Li, Lixing Zhang, Junjie Peng, Sanjun Cai, Chen Hu, Jianjun Gao, Hans Clevers, Zhen Zhang, Guoqiang Hua
Abstract
Accumulating evidence indicates that patient-derived organoids (PDOs) can predict drug responses in the clinic, but the ability of PDOs to predict responses to chemoradiation in cancer patients remains an open question. Here we generate a living organoid biobank from patients with locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiation (NACR) enrolled in a phase III clinical trial. Our co-clinical trial data confirm that rectal cancer organoids (RCOs) closely recapitulate the pathophysiology and genetic changes of corresponding tumors. Chemoradiation responses in patients are highly matched to RCO responses, with 84.43% accuracy, 78.01% sensitivity, and 91.97% specificity. These data imply that PDOs predict LARC patient responses in the clinic and may represent a companion diagnostic tool in rectal cancer treatment.
Trial registration: ClinicalTrials.gov NCT02605265.
Keywords: chemoradiation; clinical response; organoids; predict; rectal cancer.
Copyright © 2019 Elsevier Inc. All rights reserved.
Source: PubMed