Cutoff value of IC50 for drug sensitivity in patient-derived tumor organoids in colorectal cancer

Yuting Tang; Ting Wang; Yaowen Hu; Hongli Ji; Botao Yan; Xiarong Hu; Yunli Zeng; Yifan Hao; Weisong Xue; Zexin Chen; Jianqiang Lan; Yanan Wang; Haijun Deng; Chuxia Deng; Xiufeng Wu; Jun Yan

doi:10.1016/j.isci.2023.107116

Cutoff value of IC₅₀ for drug sensitivity in patient-derived tumor organoids in colorectal cancer

iScience. 2023 Jun 13;26(7):107116. doi: 10.1016/j.isci.2023.107116. eCollection 2023 Jul 21.

Authors

Yuting Tang¹, Ting Wang¹, Yaowen Hu¹, Hongli Ji¹, Botao Yan¹, Xiarong Hu¹, Yunli Zeng², Yifan Hao², Weisong Xue¹, Zexin Chen³, Jianqiang Lan³, Yanan Wang¹, Haijun Deng¹, Chuxia Deng⁴, Xiufeng Wu⁵, Jun Yan¹

Affiliations

¹ Department of General Surgery, Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Cancer, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
² Department of Oncology, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
³ Accurate International Biotechnology Limited Company, Guangzhou, Guangdong 510515, P.R. China.
⁴ Cancer Center, Faculty of Health Sciences, University of Macau, Macau, SAR of P.R. China.
⁵ Department of Surgery, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, Fujian 350014, P.R. China.

Abstract

Patient-derived tumor organoids (PDTOs) have the potential to be used to predict the patient response to chemotherapy. However, the cutoff value of the half-maximal inhibition concentration (IC₅₀) for PDTO drug sensitivity has not been validated with clinical cohort data. We established PDTOs and performed a drug test in 277 samples from 242 CRC patients who received FOLFOX or XELOX chemotherapy. After follow-up and comparison of the PDTO drug test and final clinical outcome results, the optimal IC₅₀ cutoff value for PDTO drug sensitivity was 43.26 μmol/L. This PDTO drug test-defined cutoff value could predict patient response with 75.36% sensitivity, 74.68% specificity, and 75% accuracy. Moreover, this value distinguished groups of patients with significant differences in survival benefit. Our study is the first to define the IC₅₀ cutoff value for the PDTO drug test to effectively distinguish CRC patients with chemosensitivity or nonsensitivity and predict survival benefits.

Keywords: Cancer; Drugs; Molecular modelling.