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Title: Unified framework for patient-derived, tumor-organoid-based predictive testing of standard-of-care therapies in metastatic colorectal cancer.
Austin Authors: Tan, Tao;Mouradov, Dmitri;Lee, Margaret;Gard, Grace;Hirokawa, Yumiko;Li, Shan;Lin, Cong;Li, Fuqiang;Luo, Huijuan;Wu, Kui;Palmieri, Michelle;Leong, Evelyn;Clarke, Jordan;Sakthianandeswaren, Anuratha;Brasier, Helen;Tie, Jeanne;Tebbutt, Niall C ;Jalali, Azim;Wong, Rachel;Burgess, Antony W;Gibbs, Peter;Sieber, Oliver M
Affiliation: Personalised Oncology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3052, Australia.
HIM-BGI Omics Center, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, BGI Research, Hangzhou 310000, China; Guangdong Provincial Key Laboratory of Human Disease Genomics, Shenzhen Key Laboratory of Genomics, BGI Research, Shenzhen 518083, China.
Medical Oncology
Issue Date: 19-Dec-2023
Publication information: Cell Reports. Medicine 2023-12-19; 4(12)
Abstract: Predictive drug testing of patient-derived tumor organoids (PDTOs) holds promise for personalizing treatment of metastatic colorectal cancer (mCRC), but prospective data are limited to chemotherapy regimens with conflicting results. We describe a unified framework for PDTO-based predictive testing across standard-of-care chemotherapy and biologic and targeted therapy options. In an Australian community cohort, PDTO predictions based on treatment-naive patients (n = 56) and response rates from first-line mCRC clinical trials achieve 83% accuracy for forecasting responses in patients receiving palliative treatments (18 patients, 29 treatments). Similar assay accuracy is achieved in a prospective study of third-line or later mCRC treatment, AGITG FORECAST-1 (n = 30 patients). "Resistant" predictions are associated with inferior progression-free survival; misclassification rates are similar by regimen. Liver metastases are the optimal site for sampling, with testing achievable within 7 weeks for 68.8% cases. Our findings indicate that PDTO drug panel testing can provide predictive information for multifarious standard-of-care therapies for mCRC.
DOI: 10.1016/j.xcrm.2023.101335
Journal: Cell Reports. Medicine
Start page: 101335
PubMed URL: 38118423
ISSN: 2666-3791
Type: Journal Article
Subjects: colorectal cancer
patient-derived tumor organoid
precision medicine
predictive drug testing
Colorectal Neoplasms/diagnosis
Colorectal Neoplasms/drug therapy
Colonic Neoplasms/drug therapy
Antineoplastic Agents/therapeutic use
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