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Cell stem cell

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A pancreatic cancer organoid biobank links multi-omics signatures to therapeutic response and clinical evaluation of statin combination therapy

Published:13 August 2025 DOI: 10.1016/j.stem.2025.07.008
Yunguang Li, Shijie Tang, Huan Wang, Hongwen Zhu, Yurun Lu, Yehan Zhang, Shiwei Guo, Juan He, Yikai Li, Yi Zhang, Xiaohan Shi, Yuanxiang Miao, Chaoliang Zhong, Yiqin Zhu, Yi Ju, Yuejia Liu, Maoyuan Sun, Yong Wang, Luonan Chen, Hu Zhou, Dong Gao

Abstract

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.

Substances (430)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Rapamycin 53123-88-9 C51H79NO13 1033 suppliers $9.00-$6160.00
Rapamycin 53123-88-9 C51H79NO13 1033 suppliers $9.00-$6160.00
Rapamycin 53123-88-9 C51H79NO13 1033 suppliers $9.00-$6160.00
Rapamycin 53123-88-9 C51H79NO13 1033 suppliers $9.00-$6160.00
Simvastatin 79902-63-9 C25H38O5 867 suppliers $5.00-$4900.00
Simvastatin 79902-63-9 C25H38O5 867 suppliers $5.00-$4900.00
Simvastatin 79902-63-9 C25H38O5 867 suppliers $5.00-$4900.00
Simvastatin 79902-63-9 C25H38O5 867 suppliers $5.00-$4900.00
Cytarabine 147-94-4 C9H13N3O5 793 suppliers $5.00-$1025.00
Cytarabine 147-94-4 C9H13N3O5 793 suppliers $5.00-$1025.00

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