Evidence map›Paper›PMID 38182579›Full record

ArticleCell death & disease2024

Novel dual inhibitors of PARP and HDAC induce intratumoral STING-mediated antitumor immunity in triple-negative breast cancer.

Qingyun Zhu, Qiuzi Dai, Lei Zhao, Chang Zheng, Qinyuan Li, Zigao Yuan, Lulu Li, Zhuoye Xie, Zixuan Qiu, Wenjun Huang and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
8.8field-weighted citation impact, top 2% of its field
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

24 citing papers in PubMed, 31 citations in OpenAlex.

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  15. Targeting HDAC and PARP Enhances STING-Dependent Antitumor Immunity in STING-Deficient Tumor.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
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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

14 authors at 5 institutions in 1 country.

Qingyun Zhu *The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, 421001, China.ORCID 0000-0003-1568-273X
Qiuzi Dai *State Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, 518055, China.
Lei ZhaoSchool of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China.
Chang ZhengDepartment of Breast and Thyroid Surgery, Second People's Hospital of Shenzhen, First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China.
Qinyuan LiState Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, 518055, China.
Zigao YuanState Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, 518055, China.ORCID 0000-0002-4755-2668
Lulu LiState Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, 518055, China.
Zhuoye XieState Key Laboratory of Chemical Oncogenomics, Tsinghua Shenzhen International Graduate School, Shenzhen, 518055, China.ORCID 0000-0002-9111-6003
Zixuan QiuInstitute of Biomedical Health Technology and Engineering, Shenzhen Bay Laboratory, Shenzhen, 518132, China.
Wenjun HuangSchool of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China.
Guowen LiuDepartment of Breast and Thyroid Surgery, Second People's Hospital of Shenzhen, First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China.
Xuyu ZuThe First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, 421001, China. zuxuyu0108@hotmail.com.
Bizhu ChuSchool of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China. chubz@szu.edu.cn.ORCID 0000-0002-3111-7653
Yuyang JiangSchool of Pharmacy, Shenzhen University Medical School, Shenzhen University, Shenzhen, 518055, China. jiangyy@sz.tsinghua.edu.cn.ORCID 0000-0003-3904-4855
Shenzhen University · CNShenzhen Second People's Hospital · CNChangsha Medical University · CNFirst Affiliated Hospital of University of South China · CNShenzhen Bay Laboratory · CN

Funding

National Natural Science Foundation of China (National Science Foundation of China) 22004056
6 · The paper itself

Abstract

PARP inhibitors and HDAC inhibitors have been approved for the clinical treatment of malignancies, but acquired resistance of or limited effects on solid tumors with a single agent remain as challenges. Bioinformatics analyses and a combination of experiments had demonstrated the synergistic effects of PARP and HDAC inhibitors in triple-negative breast cancer. A series of novel dual PARP and HDAC inhibitors were rationally designed and synthesized, and these molecules exhibited high enzyme inhibition activity with excellent antitumor effects in vitro and in vivo. Mechanistically, dual PARP and HDAC inhibitors induced BRCAness to restore synthetic lethality and promoted cytosolic DNA accumulation, which further activates the cGAS-STING pathway and produces proinflammatory chemokines through type I IFN-mediated JAK-STAT pathway. Moreover, these inhibitors promoted neoantigen generation, upregulated antigen presentation genes and PD-L1, and enhanced antitumor immunity when combined with immune checkpoint blockade therapy. These results indicated that novel dual PARP and HDAC inhibitors have antitumor immunomodulatory functions in triple-negative breast cancer. Novel dual PARP and HDAC inhibitors induce BRCAness to restore synthetic lethality, activating tumoral IFN signaling via the cGAS-STING pathway and inducing cytokine production, promoting neoantigen generation and presentation to enhance the immune response.

Indexed as

Triple Negative Breast NeoplasmsHistone Deacetylase InhibitorsHumansJanus KinasesNucleotidyltransferasesPoly(ADP-ribose) Polymerase InhibitorsSignal TransductionSTAT Transcription FactorsHistone Deacetylase InhibitorsJanus KinasesNucleotidyltransferasesPoly(ADP-ribose) Polymerase InhibitorsSTAT Transcription Factors

Identifiers

PMID38182579
PMCPMC10770036
OpenAlexW4390616933

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.