Patient-Derived Organoids Predict Chemoradiation Responses of Locally Advanced Rectal Cancer.,Cell Stem Cell

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Patient-Derived Organoids Predict Chemoradiation Responses of Locally Advanced Rectal Cancer.
Cell Stem Cell ( IF 19.8 ) Pub Date : 2019-11-21 , DOI: 10.1016/j.stem.2019.10.010
Ye Yao ₁ , Xiaoya Xu ₂ , Lifeng Yang ₁ , Ji Zhu ₁ , Juefeng Wan ₁ , Lijun Shen ₁ , Fan Xia ₁ , Guoxiang Fu ₂ , Yun Deng ₃ , Mengxue Pan ₂ , Qiang Guo ₂ , Xiaoxue Gao ₂ , Yuanchuang Li ₂ , Xinxin Rao ₂ , Yi Zhou ₂ , Liping Liang ₁ , Yaqi Wang ₁ , Jing Zhang ₁ , Hui Zhang ₁ , Guichao Li ₁ , Lixing Zhang ₄ , Junjie Peng ₅ , Sanjun Cai ₅ , Chen Hu ₆ , Jianjun Gao ₂ , Hans Clevers ₇ , Zhen Zhang ₁ , Guoqiang Hua ₈

Affiliation

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.
Institute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai 200032, China.
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.
Research and Early Development, Shanghai 121Biomed Inc., Shanghai 200235, China.
Department of Colorectal Cancer, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Oncode Institute, Hubrecht Institute and University Medical Center Utrecht, Uppsalalaan 8, 3584CT Utrecht, the Netherlands.
Institute of Radiation Medicine and Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.

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.

中文翻译：

患者衍生的类器官可预测局部晚期直肠癌的化学放射反应。

越来越多的证据表明，患者衍生的类器官（PDO）可以预测临床中的药物反应，但是PDO预测癌症患者对化学放射反应的能力仍然是一个悬而未决的问题。在这里，我们从参与第三阶段临床试验的新辅助化学放疗（NACR）的局部晚期直肠癌（LARC）患者中产生了一个活的类器官生物库。我们的临床试验数据证实，直肠癌类器官（RCO）可以密切概括相应肿瘤的病理生理和遗传变化。患者的化学放射反应与RCO反应高度匹配，准确度为84.43％，敏感性为78.01％，特异性为91.97％。这些数据表明，PDO在临床上可预测LARC患者的反应，并可能代表直肠癌治疗中的辅助诊断工具。

更新日期：2019-11-22

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