A pancreatic cancer organoid biobank links multi-omics signatures to therapeutic response and clinical evaluation of statin combination therapy
文献类型：期刊论文
| 作者 | Li, Yunguang1,2; Tang, Shijie2; Wang, Huan3; Zhu, Hongwen4,5; Lu, Yurun6,7; Zhang, Yehan2; Guo, Shiwei3; He, Juan1; Li, Yikai3; Zhang, Yi8 |
| 刊名 | CELL STEM CELL
 |
| 出版日期 | 2025-09-04 |
| 卷号 | 32期号:9页码:36 |
| ISSN号 | 1934-5909 |
| DOI | 10.1016/j.stem.2025.07.008 |
| 英文摘要 | Chemotherapy remains the primary treatment for pancreatic ductal adenocarcinoma (PDAC), but most patients ultimately develop resistance. Here, we established 260 pancreatic cancer organoid lines, followed by extensive multi-omics profiling and therapeutic sensitivity assessments. Integrated analyses uncovered 6 novel coding and 35 noncoding driver candidates. We discovered 2,794 multi-omics features associated with drug sensitivity and 322 features linked to radiation sensitivity. Pharmacogenomic analyses revealed that chemoresistant organoids exhibited enrichment in protein glycosylation and cholesterol metabolism pathways. Notably, statins effectively targeted chemoresistant PDAC organoids. Statin treatment attenuated protein glycosylation, cholesterol levels, and the epithelial-to-mesenchymal transition (EMT) signature in PDAC organoids. We conducted a single-center, single-arm, phase 2 clinical trial (NCT06241352) combining atorvastatin with chemotherapy in patients with advanced pancreatic cancer. Among 37 patients, 26 (70.3%) demonstrated a response, with tumor markers decreasing by more than 20%, suggesting durable responses and potential clinical benefits in this challenging patient population. |
| WOS关键词 | MOLECULAR SIGNATURES ; BREAST-CANCER ; SOLID TUMORS ; CELL ; MUTATIONS ; LANDSCAPE ; SUBTYPES ; PATHWAY ; DNA ; ACTIVATION |
| 资助项目 | National Science Fund for Distinguished Young Scholars[32125013] ; National Key Research and Development Program of China[2020YFA05 09000] ; National Key Research and Development Program of China[2023YFC2506400] ; National Key Research and Development Program of China[2024YFF0507402] ; National Key Research and Development Program of China[2025YFF1207900] ; National Key Research and Development Program of China[2022YFA1004800] ; National Natural Science Foundation of China[92253304] ; National Natural Science Foundation of China[82303257] ; National Natural Science Foundation of China[82303575] ; National Natural Science Foundation of China[82172712] ; National Natural Science Foundation of China[82473166] ; National Natural Science Foundation of China[82172589] ; National Natural Science Foundation of China[82303496] ; National Natural Science Foundation of China[22425703] ; National Natural Science Foundation of China[T2341007] ; National Natural Science Foundation of China[T2350003] ; National Natural Science Foundation of China[12131020] ; National Natural Science Foundation of China[12025107] ; National Natural Science Foundation of China[12326610] ; Basic Frontier Science Research Program of Chinese Academy of Sciences[ZDBS-LY-SM015] ; Shanghai Science and Technology Committee[24ZR1492900] ; Shanghai Science and Technology Committee[23JS1401300] ; Shanghai Municipal Science and Technology Major Project ; Innovative Research Team of Highlevel Local Universities in Shanghai[SHSMUZDCX20211800] ; Shanghai Science and Technology Innovation Action Plan[23Y41900200] ; Naval Medical University[25TPSL0008] ; Changhai Hospital of Naval Medical University[2024LYA04] ; Changhai Hospital of Naval Medical University[GH145-07] ; Changhai Hospital of Naval Medical University[2020YXK005] ; Changhai Hospital of Naval Medical University[2024XB006] ; National Key Research and Development Program ; Zhejiang Province Vanguard Goose-Leading Initiative[2025C01114] ; Hangzhou Institute for advanced study of UCAS[2024HIAS-P004] ; CAS Project for Young Scientists in Basic Research[YSBR-077] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB0830000] ; [2022YFA1302902] |
| WOS研究方向 | Cell Biology |
| 语种 | 英语 |
| WOS记录号 | WOS:001566593400003 |
| 出版者 | CELL PRESS |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/321414]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Wang, Yong; Chen, Luonan; Zhou, Hu; Jin, Gang; Gao, Dong |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Biochem & Cell Biol, Ctr Excellence Mol Cell Sci, Key Lab Multicell Syst,Shanghai Key Lab Mol Androl, Shanghai 200031, Peoples R China 2.Shanghai Jiao Tong Univ, Sch Med, Shanghai Gen Hosp, Shanghai 200025, Peoples R China 3.Second Mil Med Univ, Changhai Hosp, Dept Hepatobiliary Pancreat Surg, Naval Med Univ, Shanghai 200433, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, Dept Analyt Chem, State Key Lab Drug Res, Shanghai 201203, Peoples R China 5.Guangzhou Univ, Precise Genome Engn Ctr, Sch Life Sci, Guangzhou 510006, Peoples R China 6.Chinese Acad Sci, Acad Math & Syst Sci, State Key Lab Math Sci, Beijing 100190, Peoples R China 7.Chinese Acad Sci, Univ Chinese Acad Sci, Sch Math, Beijing 100049, Peoples R China 8.Chongqing Med Univ, Affiliated Hosp 1, Chongqing, Peoples R China 9.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China 10.Chinese Acad Sci, Hangzhou Inst Adv Study, Key Lab Syst Hlth Sci Zhejiang Prov, Sch Life Sci,Univ Chinese Acad Sci, Hangzhou 310024, Peoples R China |
| 推荐引用方式 GB/T 7714 | Li, Yunguang,Tang, Shijie,Wang, Huan,et al. A pancreatic cancer organoid biobank links multi-omics signatures to therapeutic response and clinical evaluation of statin combination therapy[J]. CELL STEM CELL,2025,32(9):36. |
| APA | Li, Yunguang.,Tang, Shijie.,Wang, Huan.,Zhu, Hongwen.,Lu, Yurun.,...&Gao, Dong.(2025).A pancreatic cancer organoid biobank links multi-omics signatures to therapeutic response and clinical evaluation of statin combination therapy.CELL STEM CELL,32(9),36. |
| MLA | Li, Yunguang,et al."A pancreatic cancer organoid biobank links multi-omics signatures to therapeutic response and clinical evaluation of statin combination therapy".CELL STEM CELL 32.9(2025):36. |
入库方式： OAI收割
来源：上海药物研究所
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