Evidence map›Paper›PMID 41881024›Full record

ArticleCell reports. Medicine2026

Targeting the ferritinophagy-lysosome axis as a therapeutic vulnerability in gastroenteropancreatic neuroendocrine tumors.

Yizhi Cao, Caleb Cheng, Yitong Yin, Sarah N Yee, Yang Zheng, Somnath Mahapatra, Radha Paturu, Andrej Coleski, Shannon VanAken, Fan Yang and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

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

22 authors.

Yizhi CaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
Caleb ChengMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Cellular and Molecular Biology Program, University of Michigan, Ann Arbor, MI, USA.
Yitong YinMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Sarah N YeeMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Yang ZhengMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Somnath MahapatraMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Radha PaturuMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Andrej ColeskiMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Shannon VanAkenMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Fan YangMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Rüya PakkanMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Yi ZhaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.
Rupam BhattacharyyaMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Stephanie J MinerMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Xuhong CaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Rahul MannanMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA.
Chungen LiState Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, P.R. China.
Vaibhav SahaiRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
Ke DingState Key Laboratory of Chemical Biology, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, P.R. China.
Costas A LyssiotisRogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA; Department of Internal Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, USA.
Arul M ChinnaiyanMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Howard Hughes Medical Institute, University of Michigan, Ann Arbor, MI, USA; Department of Urology, University of Michigan, Ann Arbor, MI, USA. Electronic address: arul@med.umich.edu.
Yuanyuan QiaoMichigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI, USA; Rogel Cancer Center, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA. Electronic address: qiaoy@med.umich.edu.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

mTOR inhibitors (mTORis) are Food and Drug Administration (FDA)-approved therapies for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs), yet their clinical efficacy is often limited by transient responses and acquired resistance. To uncover sensitizing co-targets, we conduct a kinome-wide CRISPR-Cas9 screen, identifying the lipid kinase PIKfyve as a key vulnerability in GEP-NETs. PIKfyve is overexpressed and functionally linked to the regulation of lipid biosynthesis through the mTOR-SREBP1 axis. Mechanistically, PIKfyve inhibition impairs lysosome-mediated ferritin degradation, amplifying metabolic stress triggered by mTORi-induced ferritinophagy. Co-inhibition of mTOR and PIKfyve synergistically disrupts lipid and iron metabolism, leading to enhanced tumor suppression and improved survival in preclinical GEP-NET models. These findings nominate PIKfyve as a metabolic co-target to overcome mTORi resistance, offering a rationale for combination therapies in mTOR-driven malignancies.

Indexed as

AutophagyIntestinal NeoplasmsLysosomesNeuroendocrine TumorsPancreatic NeoplasmsStomach NeoplasmsAnimalsCell Line, TumorHumansLipid MetabolismMiceMTOR InhibitorsPhosphatidylinositol 3-KinasesSignal TransductionTOR Serine-Threonine KinasesMTOR InhibitorsMTOR protein, humanPhosphatidylinositol 3-KinasesTOR Serine-Threonine Kinasesferritinophagygastroenteropancreatic neuroendocrine tumorlipid metabolismlysosomemTORPIKfyve

Identifiers

PMID41881024
PMCPMC13130658

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.