Unified framework for patient-derived, tumor-organoid-based predictive testing of standard-of-care therapies in metastatic colorectal cancer

Tan, T; Mouradov, D; Lee, M; Gard, G; Hirokawa, Y; Li, S; Lin, C; Li, F; Luo, H; Wu, K; Palmieri, M; Leong, E; Clarke, J; Sakthianandeswaren, A; Brasier, H; Tie, J; Tebbutt, NC; Jalali, A; Wong, R; Burgess, AW; Gibbs, P; Sieber, OM

Author(s): Tan, T; Mouradov, D; Lee, M; Gard, G; Hirokawa, Y; Li, S; Lin, C; Li, F; Luo, H; Wu, K; Palmieri, M; Leong, E; Clarke, J; Sakthianandeswaren, A; Brasier, H; Tie, J; Tebbutt, NC; Jalali, A; Wong, R; Burgess, AW; Gibbs, P; Sieber, OM;
Details: Publication Year 2023-12-19,Volume 4,Issue #12,Page 101335
Journal Title: Cell Reports Medicine
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.
Publisher: Elsevier
Keywords: Humans; *Colorectal Neoplasms/diagnosis/drug therapy; Prospective Studies; Australia; *Colonic Neoplasms/drug therapy; *Antineoplastic Agents/therapeutic use; colorectal cancer; patient-derived tumor organoid; precision medicine; predictive drug testing
Research Division(s): Personalised Oncology
PubMed ID: 38118423
Publisher's Version: https://doi.org/10.1016/j.xcrm.2023.101335
Open Access at Publisher's Site: https://doi.org/10.1016/j.xcrm.2023.101335
Terms of Use/Rights Notice: Refer to copyright notice on published article.
Documents: PIIS2666379123005529.pdf - (8.76MB, application/pdf)

Creation Date: 2024-01-16 09:41:00

Last Modified: 2024-01-16 09:54:03