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

doi:10.1016/j.stem.2019.10.010

Patient-Derived Organoids Predict Chemoradiation Responses of Locally Advanced Rectal Cancer

Cell Stem Cell. 2020 Jan 2;26(1):17-26.e6. doi: 10.1016/j.stem.2019.10.010. Epub 2019 Nov 21.

Authors

Ye Yao¹, Xiaoya Xu², Lifeng Yang¹, Ji Zhu¹, Juefeng Wan¹, Lijun Shen¹, Fan Xia¹, Guoxiang Fu², Yun Deng³, Mengxue Pan², Qiang Guo², Xiaoxue Gao², Yuanchuang Li², Xinxin Rao², Yi Zhou², Liping Liang¹, Yaqi Wang¹, Jing Zhang¹, Hui Zhang¹, Guichao Li¹, Lixing Zhang⁴, Junjie Peng⁵, Sanjun Cai⁵, Chen Hu⁶, Jianjun Gao², Hans Clevers⁷, Zhen Zhang⁸, Guoqiang Hua⁹

Affiliations

¹ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
² Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China.
³ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Cancer Institute, Fudan University Shanghai Cancer Center, Shanghai 230032, China.
⁴ Research and Early Development, Shanghai 121Biomed Inc., Shanghai 200235, China.
⁵ Department of Colorectal Cancer, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
⁶ Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
⁷ Oncode Institute, Hubrecht Institute and University Medical Center Utrecht, Uppsalalaan 8, 3584CT Utrecht, the Netherlands.
⁸ Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China. Electronic address: [email protected].
⁹ Institute of Radiation Medicine and Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China. Electronic address: [email protected].

PMID: 31761724
DOI: 10.1016/j.stem.2019.10.010

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chemoradiotherapy
Humans
Neoadjuvant Therapy
Organoids*
Rectal Neoplasms* / therapy

Associated data

ClinicalTrials.gov/NCT02605265