Personalized drug screening using patient-derived organoid and its clinical relevance in gastric cancer
- Cell Rep Med. 2024 Jul 16;5(7):101627. doi: 10.1016/j.xcrm.2024.101627.
- 1. Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- 2. Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- 3. Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- 4. Department of Gastrointestinal Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
- 5. Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China.
- 6. Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore.
- 7. Department of Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: [email protected].
- 8. Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China; Department of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong SAR, China. Electronic address: [email protected].
- 9. Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: [email protected].
The efficacy of chemotherapy varies significantly among patients with gastric Cancer (GC), and there is currently no effective strategy to predict chemotherapeutic outcomes. In this study, we successfully establish 57 GC patient-derived organoids (PDOs) from 73 patients with GC (78%). These organoids retain histological characteristics of their corresponding primary GC tissues. GC PDOs show varied responses to different chemotherapeutics. Through RNA Sequencing, the upregulation of tumor suppression genes/pathways is identified in 5-fluorouracil (FU)- or oxaliplatin-sensitive organoids, whereas genes/pathways associated with proliferation and invasion are enriched in chemotherapy-resistant organoids. Gene expression biomarker panels, which could distinguish sensitive and resistant patients to 5-FU and oxaliplatin (area under the dose-response curve [AUC] >0.8), are identified. Moreover, the drug-response results in PDOs are validated in patient-derived organoids-based xenograft (PDOX) mice and are consistent with the actual clinical response in 91.7% (11/12) of patients with GC. Assessing chemosensitivity in PDOs can be utilized as a valuable tool for screening chemotherapeutic drugs in patients with GC.