Evidence map›Paper›PMID 41476110›Full record

ArticleNeuro-oncology2026

VITA-GBM: EPIC-0502-driven HIF1α degradation overcomes bevacizumab resistance and synergizes with TMZ in glioblastoma.

Yaqing Ding, Qi Zhan, Longtao Cui, Xiaoteng Cui, Yilin Zhao, Qixue Wang, Biao Hong, Yanping Huang, Dongyuan Su, Chunchao Cheng and 5 more

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Article in Neuro-oncology, 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

15 authors.

Yaqing DingLaboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (Y.D., Q.Z., L.C., X.C., Y.Z., Q.W., B.H., Y.H., D.S., C.C., H.X., S.L., X.Z., Y.L., C.K.).
Qi ZhanLaboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (Y.D., Q.Z., L.C., X.C., Y.Z., Q.W., B.H., Y.H., D.S., C.C., H.X., S.L., X.Z., Y.L., C.K.).
Longtao CuiLaboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (Y.D., Q.Z., L.C., X.C., Y.Z., Q.W., B.H., Y.H., D.S., C.C., H.X., S.L., X.Z., Y.L., C.K.).
Xiaoteng CuiLaboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (Y.D., Q.Z., L.C., X.C., Y.Z., Q.W., B.H., Y.H., D.S., C.C., H.X., S.L., X.Z., Y.L., C.K.).
Yilin ZhaoLaboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (Y.D., Q.Z., L.C., X.C., Y.Z., Q.W., B.H., Y.H., D.S., C.C., H.X., S.L., X.Z., Y.L., C.K.).
Qixue WangLaboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (Y.D., Q.Z., L.C., X.C., Y.Z., Q.W., B.H., Y.H., D.S., C.C., H.X., S.L., X.Z., Y.L., C.K.).
Biao HongLaboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (Y.D., Q.Z., L.C., X.C., Y.Z., Q.W., B.H., Y.H., D.S., C.C., H.X., S.L., X.Z., Y.L., C.K.).
Yanping HuangLaboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (Y.D., Q.Z., L.C., X.C., Y.Z., Q.W., B.H., Y.H., D.S., C.C., H.X., S.L., X.Z., Y.L., C.K.).
Dongyuan SuLaboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (Y.D., Q.Z., L.C., X.C., Y.Z., Q.W., B.H., Y.H., D.S., C.C., H.X., S.L., X.Z., Y.L., C.K.).
Chunchao ChengLaboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (Y.D., Q.Z., L.C., X.C., Y.Z., Q.W., B.H., Y.H., D.S., C.C., H.X., S.L., X.Z., Y.L., C.K.).
Hanyi XuLaboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (Y.D., Q.Z., L.C., X.C., Y.Z., Q.W., B.H., Y.H., D.S., C.C., H.X., S.L., X.Z., Y.L., C.K.).
Siwen LiangLaboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (Y.D., Q.Z., L.C., X.C., Y.Z., Q.W., B.H., Y.H., D.S., C.C., H.X., S.L., X.Z., Y.L., C.K.).
Xun ZhaoLaboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (Y.D., Q.Z., L.C., X.C., Y.Z., Q.W., B.H., Y.H., D.S., C.C., H.X., S.L., X.Z., Y.L., C.K.).
Yuhao LiuLaboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (Y.D., Q.Z., L.C., X.C., Y.Z., Q.W., B.H., Y.H., D.S., C.C., H.X., S.L., X.Z., Y.L., C.K.).
Chunsheng KangLaboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Key Laboratory of Post-Neuro Injury Neuro-Repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin, China (Y.D., Q.Z., L.C., X.C., Y.Z., Q.W., B.H., Y.H., D.S., C.C., H.X., S.L., X.Z., Y.L., C.K.).ORCID 0000-0002-3255-3369

Funding

National Key R&D Program of China 2023YFC2510000National Natural Science Foundation of ChinaNSFC 82403947NSFC 82473194
6 · The paper itself

Abstract

backgroundGlioblastoma (GBM) is characterized by extensive tissue hypoxia. This hypoxic microenvironment drives chemoresistance and promotes aberrant vascularization, critically limiting the efficacy of temozolomide (TMZ) and bevacizumab (BEV). Here, we report EPIC-0502, a novel small-molecule competitive antagonist that inhibits hypoxia signaling while sensitizing GBM to both TMZ and BEV.

methodsEPIC-0502 was identified through molecular dynamics simulation. Its target blocking effect was validated via non-targeted metabolomics, stable isotope tracing-based metabolic flux analysis, and pull-down assays. The mechanisms underlying EPIC-0502 activity were elucidated by Western Blot (WB), Co-Immunoprecipitation (Co-IP), ELISA, Seahorse assays, and Immunofluorescence (IF). The sensitizing effects of EPIC-0502 on TMZ and BEV were evaluated in orthotopic GBM models.

resultsEPIC-0502 inhibited α-ketoglutarate (α-KG) to succinate conversion, depleting cytoplasmic succinate levels and inhibiting phosphoglycerate kinase 1 (PGK1) succinylation and phosphorylation, which significantly attenuated glycolysis. Furthermore, EPIC-0502 destabilized Hypoxia-inducible factor 1 alpha (HIF1α) by promoting hydroxylation-dependent ubiquitination, while impairing its transcriptional activity. Through HIF1α degradation, EPIC-0502 enhanced GBM sensitivity to TMZ via E2F1 downregulation and reversed hypoxia-induced vascular endothelial growth factor A (VEGFA) overexpression, potentiating the antiangiogenic efficacy of BEV. Collectively, these actions enable EPIC-0502 to synergistically enhance the therapeutic efficacy of TMZ/BEV combination.

conclusionsBased on EPIC-0502-driven HIF1α degradation that overcomes BEV resistance and synergizes with TMZ, we propose the novel VITA-GBM regimen comprising: Vascular targeting (BEV), Inhibition of hypoxia signaling (EPIC-0502), TMZ chemotherapy, and Alignment of synergistic mechanisms. This strategy enhances the efficacy of first-line therapies and provides a promising approach to improve overall survival in GBM patients.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBevacizumabBrain NeoplasmsDrug Resistance, NeoplasmGlioblastomaHypoxia-Inducible Factor 1, alpha SubunitTemozolomideAnimalsDrug SynergismHumansMiceMice, NudeTumor Cells, CulturedXenograft Model Antitumor AssaysBevacizumabHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitTemozolomidebevacizumabglioblastomaHIF1αprotein succinylationTMZ sensitization

Identifiers

PMID41476110
PMCPMC13128469

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Registered trials

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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.