Article in Cancer research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
2 · The registry
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
5 · Who and what money
Authors and funding
13 authors.
Shaobo ZhangState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID 0000-0001-5413-5064
Hao YuanDepartment of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.ORCID 0009-0007-4848-3354
Muzi GuoDepartment of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.ORCID 0009-0007-3750-0817
Zhijun ZhouDepartment of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.ORCID 0000-0003-2226-2223
Yumeng HuState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID 0009-0000-8078-6127
Gaoyuan LvState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID 0000-0002-4264-4803
Haoran QiState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID 0009-0003-3273-6012
Yuanyuan GuoState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID 0000-0002-2944-9595
Jing HanState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID 0009-0004-5023-1912
Michael S BronzeDepartment of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.ORCID 0000-0002-8770-0872
Courtney W HouchenDepartment of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.ORCID 0000-0003-2487-5242
Min LiDepartment of Medicine, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma.ORCID 0000-0002-3971-9130
Mingyang LiuState Key Laboratory of Molecular Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.ORCID 0009-0005-8763-5192
Funding
Chinese Academy of Medical Sciences (CAMS) 2022-RC310-01Chinese Academy of Medical Sciences Initiative for Innovative Medicine () 2023-I2M-2-004Fundamental Research Funds for the Central Universities (Fundamental Research Fund for the Central Universities) 3332024047National Key Research and Development Program of China (NKPs) 2023YFC2413200National Key Research and Development Program of China (NKPs) 2023YFC2413205National Natural Science Foundation of China (NSFC) 82273452National Natural Science Foundation of China (NSFC) 82403706National Natural Science Foundation of China (NSFC) 92474301National Science and Technology Major Project () 2025ZD0552400/2025ZD0552405National Science and Technology Major Project () 2025ZD0552500/2025ZD0552504Postdoctoral Research Foundation of China (China Postdoctoral Research Foundation) GZC20240140
6 · The paper itself
Abstract
Pancreatic cancer remains one of the deadliest malignancies, with gemcitabine-based chemotherapy as the mainstay treatment for most patients, yet resistance emerges almost universally. A defining feature of pancreatic cancer is its dense, fibroblast-rich stroma, in which heterogeneous cancer-associated fibroblasts (CAF) actively shape tumor biology and therapeutic response. Here, we elucidated a stromal-metabolic mechanism through which chemoresistant CAFs confer gemcitabine resistance. We identified a subset of mitophagy-competent CAFs that enhanced pancreatic cancer gemcitabine resistance. The epithelial-mesenchymal transition transcription factor ZEB1 acts as a master regulator of this CAF-driven chemoresistance program, being upregulated and epigenetically activated via SETD1A-mediated H3K4 methylation in gemcitabine-resistant CAFs. ZEB1 promotes BNIP3-mediated mitophagy in CAFs, leading to increased nucleotides secretion, which competitively inhibited gemcitabine incorporation into cancer cells while simultaneously supplying pyrimidine metabolism substrates for pyrimidine metabolism. Concurrently, ZEB1 transcriptionally activated CXCL8, engaging the CXCR1/2-MEK/ERK pathway in tumor cells and further augmenting pyrimidine metabolism via the RRM1/E2F1/G6PD axis, collectively diminishing gemcitabine cytotoxicity. Notably, combined inhibition of CXCR1/2 or G6PD with gemcitabine robustly suppressed tumor growth and restored chemosensitivity both in vitro and in vivo. These findings uncover a key stromal-metabolic axis in pancreatic cancer, linking mitophagy CAF activity to metabolic remodeling in tumor cells and identifying ZEB1 and its downstream network as actionable targets to overcome chemoresistance. SIGNIFICANCE: ZEB1 reprograms mitophagy-competent CAFs to promote gemcitabine resistance by enhancing nucleotide supply and activating tumor pyrimidine metabolism, supporting therapeutic targeting of the ZEB1-CXCL8-pyrimidine axis in pancreatic cancer.
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.
Mitophagy-Competent Cancer-Associated Fibroblasts Fuel Chemoresistance by Rewiring Pyrimidine Metabolism in Pancreatic Cancer. · full record | Socratic