Evidence map›Paper›PMID 41758952›Full record

ArticleScience advances2026

PROTAC-based synthetic lethality strategy endogenously activates systemic STING to boost antitumor immunity.

Ye Liu, Maolin Jiang, Mengchao Ding, Ihsan Ullah, Haiyang Wang, Wenjiao Xie, Kewei Wang, Youyong Yuan

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 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

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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

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

8 authors.

Ye LiuSchool of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 511442, P.R. China.ORCID 0009-0008-2420-2156
Maolin JiangSchool of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 511442, P.R. China.
Mengchao DingSchool of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 511442, P.R. China.
Ihsan UllahSchool of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 511442, P.R. China.ORCID 0000-0003-1441-2105
Haiyang WangNational Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou 510006, P.R. China.
Wenjiao XieSchool of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 511442, P.R. China.
Kewei WangKey Laboratory of Biomaterials of Guangdong Higher Education Institutes, Engineering Technology Research Center of Drug Carrier of Guangdong, Department of Biomedical Engineering and MOE Key Laboratory of Tumor Molecular Biology, Jinan University, Guangzhou 510632, China.ORCID 0009-0001-2366-1376
Youyong YuanSchool of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou 511442, P.R. China.ORCID 0000-0003-2784-3780

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Activation of the stimulator of interferon genes (STING) pathway drives natural killer (NK) cells and T cells to orchestrate multidimensional antitumor immune responses. While cytosolic DNA accumulation represents a superior endogenous strategy for STING activation, DNA repair machinery substantially constrains its immunogenic potential. Here, we propose a promising therapeutic strategy that leverages proteolysis-targeting chimera (PROTAC)-mediated degradation of PARP1 [poly(ADP-ribose) polymerase 1] and BRD4 (bromodomain-containing protein 4) to induce synthetic lethality, thereby disrupting DNA repair machinery that drives nuclear-to-cytosolic DNA leakage, surpassing the STING activation threshold to ignite cGAS-STING-mediated innate immunity. Our strategy demonstrates superior antitumor efficacy across multiple tumor models, eliciting robust CD8

Indexed as

Membrane ProteinsNeoplasmsSynthetic Lethal MutationsAnimalsCD8-Positive T-LymphocytesCell Line, TumorcGAS-STING Signaling PathwayCyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseDNA RepairHost-Directed TherapyHumansImmunity, InnateKiller Cells, NaturalMiceNucleotidyltransferasesPoly (ADP-Ribose) Polymerase-1Cyclic Guanosine Monophosphate-Adenosine Monophosphate SynthaseMembrane ProteinsNucleotidyltransferasesPoly (ADP-Ribose) Polymerase-1Proteolysis Targeting ChimeraSTING1 protein, humanSting1 protein, mouseSTING Protein

Identifiers

PMID41758952
PMCPMC12947880

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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.