Evidence map›Paper›PMID 42384695›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2026

Synthetic essentiality of TRAIL/TNFSF10 in VHL-deficient renal cell carcinoma.

Xuechun Wang, Yujing Qin, Loan D Duong, Minzhi Liang, Adrian Chao, Rossella Parrotta, Yaoyin Li, Paresh Kumar Purohit, Yihao Fang, Guoqiang Liu and 10 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

20 authors.

Xuechun Wang *Department of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.
Yujing Qin *Department of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.ORCID 0009-0007-5519-2803
Loan D DuongDepartment of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.
Minzhi LiangDepartment of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.ORCID 0009-0000-4665-5959
Adrian ChaoDepartment of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.ORCID 0009-0008-1226-0631
Rossella ParrottaSchool of Chemical and Biological Sciences, University of Galway, Galway H91 TK33, Ireland.
Yaoyin LiDepartment of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.
Paresh Kumar PurohitDepartment of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.
Yihao FangDepartment of Applied and Computational Mathematics and Statistics, University of Notre Dame, Notre Dame, IN 46556.
Guoqiang LiuDepartment of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.
Jianping HeDepartment of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.ORCID 0009-0001-6177-4179
Jiling WenDepartment of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.
Yan LiuDepartment of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.ORCID 0000-0003-2512-239X
Yuting ZhangDepartment of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.
Junling ZhaoDepartment of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.
Nipuni BarupalaDepartment of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.ORCID 0000-0002-7630-3089
Zachary T SchaferDepartment of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.ORCID 0000-0001-9227-3118
Xuemin LuDepartment of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.
Eva SzegezdiSchool of Chemical and Biological Sciences, University of Galway, Galway H91 TK33, Ireland.ORCID 0000-0002-5708-3535
Xin LuDepartment of Biological Sciences, Boler-Parseghian Center for Rare Diseases, Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN 46556.ORCID 0000-0002-0284-6478

Funding

Mitophagy-Mediated Cell Death in Mammary TumorigenesisR01CA262439 · NCI · UNIVERSITY OF NOTRE DAME · PI SCHAFER, ZACHARY T. · 2021 to 2025
$2.1M
Converting Cold to Hot Tumor Microenvironment in Prostate Cancer by Targeting Chromatin EffectorR01CA248033 · NCI · UNIVERSITY OF NOTRE DAME · PI LU, XIN · 2020 to 2024
$1.8M
Immunosuppression and Metabolic Rewiring in Tumor-infiltrating NeutrophilsR01CA280097 · NCI · UNIVERSITY OF NOTRE DAME · PI Xin Lu · 2023 to 2026
$1.4M
Boler Family Foundation Endowment fundHHS | NIH (NIH) R01CA248033 R01CA280097 and R01CA297220HHS | NIH (NIH) R01CA262439NCI NIH HHS R01 CA248033NCI NIH HHS R01 CA262439NCI NIH HHS R01 CA280097University of Notre Dame (ND) Naughton Faculty Research Accelerator ProgramU.S. Department of Defense (DOD) W81XWH2010312 W81XWH2010332 HT94252310010 and HT94252310613VHL Alliance (VHLA) Competitive Research Grant Program
6 · The paper itself

Abstract

Clear cell renal cell carcinoma (ccRCC) is the most common and aggressive subtype of kidney cancer. Loss of von Hippel-Lindau (VHL) and the consequent activation of hypoxia-inducible factor-α (HIFα, especially HIF2α) plays an essential role in ccRCC initiation and progression. The VHL-HIF2α axis as the main driver for ccRCC may present specific opportunities to control the disease by cotargeting HIF2α with belzutifan and another vulnerability. This study elucidates the synthetic essentiality of TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) in VHL-deficient ccRCC. Upregulated in ccRCC in a VHL-HIF2α-dependent manner, TRAIL is selectively essential in ccRCC cells, promoting cell proliferation by activating the p38 MAPK pathway and facilitating G1/S phase transition. Depletion of endogenous TRAIL or inhibition of HIF2α with belzutifan sensitizes ccRCC cell and tumor models to recombinant TRAIL, presenting a promising avenue for combination therapy in ccRCC.

Indexed as

Carcinoma, Renal CellKidney NeoplasmsTNF-Related Apoptosis-Inducing LigandVon Hippel-Lindau Tumor Suppressor ProteinAnimalsBasic Helix-Loop-Helix ProteinsCell Line, TumorCell ProliferationEndothelial PAS Domain-Containing Protein 1HumansMicep38 Mitogen-Activated Protein KinasesBasic Helix-Loop-Helix ProteinsEndothelial PAS Domain-Containing Protein 1p38 Mitogen-Activated Protein KinasesTNF-Related Apoptosis-Inducing LigandTNFSF10 protein, humanVHL protein, humanVon Hippel-Lindau Tumor Suppressor ProteinbelzutifanHIF2αrenal cell carcinomaTRAILVHL

Identifiers

PMID42384695
PMCPMC13343000

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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.