Evidence map›Paper›PMID 40316566›Full record

ArticleScientific reports2025

PARP inhibitors elicit a cellular senescence mediated inflammatory response in homologous recombination proficient cancer cells.

Misato Kamii, Ryo Kamata, Hitoshi Saito, Gaku Yamamoto, Chiaki Mashima, Toyohiro Yamauchi, Takehiro Nakao, Yuta Sakae, Tomoko Yamamori-Morita, Kazuki Nakai and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing 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

7 citing papers in PubMed.

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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.

Misato Kamii *Division of Collaborative Research and Developments, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Ryo Kamata *Division of Collaborative Research and Developments, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. rykamat@east.ncc.go.jp.
Hitoshi SaitoDivision of Collaborative Research and Developments, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Gaku YamamotoDivision of Collaborative Research and Developments, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Chiaki MashimaDivision of Collaborative Research and Developments, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Toyohiro YamauchiDivision of Collaborative Research and Developments, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Takehiro NakaoDivision of Collaborative Research and Developments, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Yuta SakaeDivision of Collaborative Research and Developments, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Tomoko Yamamori-MoritaDivision of Collaborative Research and Developments, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Kazuki NakaiDivision of Collaborative Research and Developments, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Yumi HakozakiDivision of Collaborative Research and Developments, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
Masataka TakenakaDepartment of Obstetrics and Gynecology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo, 105-8461, Japan.
Aikou OkamotoDepartment of Obstetrics and Gynecology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-Ku, Tokyo, 105-8461, Japan.
Akihiro OhashiDivision of Collaborative Research and Developments, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. aohashi@east.ncc.go.jp.

Funding

Grant-in-Aid for Research Activity Start-up 24K23370Grants-in-Aid for Fostering Joint International Research (B) 20KK0187Grants-in-Aid for Scientific Research (C) 23K06708the Grants-in-Aid for Scientific Research (B) 20H03541
6 · The paper itself

Abstract

Poly (ADP-ribose) polymerase (PARP) inhibitors have improved the prognosis of homologous recombination deficient (HRD) ovarian cancer (OC), while effective therapeutic strategies for HR-proficient (HRP) OC still need to be established. This study investigates senescence-mediated inflammation as a novel mechanism of action for PARP inhibitors in HRP cancers. Transcriptome analyses were performed in olaparib-treated HeLa cells as a HRP model. Interferon regulatory factor-Lucia luciferase (IRF-Luc) reporter activity was assessed. The effects of PARP inhibitors on senescence-like phenotypes were assessed in seven HRP cancer cell lines, based on morphological changes, senescence-associated β-galactosidase (SA-β-GAL) activity, cellular granularity, and senescence-associated secretory phenotype (SASP)-related gene expression. Peripheral blood mononuclear cell (PBMC) migration assays were also performed with the conditioned medium in treatment with the PARP inhibitor. Transcriptome analyses revealed numbers of inflammatory cytokine- and chemokine-related pathways were significantly upregulated in olaparib-treated HeLa cells, which were confirmed by IRF-Luc reporter assays. The PARP inhibitors induced senescent phenotypes in HRP cancer cell lines: flattened and enlarged morphology, increased SA-β-GAL activity, elevated cellular granularity, and upregulated expressions of SASP-related genes (e.g., IL1B, IL6, and CXCL10). Furthermore, in vitro migration assays revealed that PARP inhibitor-treated HRP cancer cells attracted PBMCs more abundantly, suggesting the potential for recruiting immune cells to HRP cancer cells through senescence-mediated immunological activation. Our findings suggest that PARP inhibitors recruit immune cells to HRP cancer cells, potentially activating immune responses in the tumor microenvironment, providing new insights into the clinical benefits of PARP inhibitors in immunotherapy for patients with HRP OC.

Indexed as

Cellular SenescenceHomologous RecombinationInflammationPoly(ADP-ribose) Polymerase InhibitorsCell Line, TumorCytokinesFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticHeLa CellsHumansLeukocytes, MononuclearPhthalazinesPiperazinesSenescence-Associated Secretory PhenotypeCytokinesolaparibPhthalazinesPiperazinesPoly(ADP-ribose) Polymerase InhibitorsHomologous recombination-proficient (HRP) cancerOvarian cancer (OC)Poly (ADP-ribose) polymerase (PARP) inhibitorsSenescence-associated secretory phenotype (SASP)

Identifiers

PMID40316566
PMCPMC12048520

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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.