Evidence map›Paper›PMID 42628527›Full record

ArticleCell reports. Medicine2026

PARP inhibition enhances the antitumor activity of HER3-DXd in non-small cell lung cancer.

Linh Lin, Narges Moradi, Iris A Lähdeniemi, Hanna K Laitinen, Bassel Alsaed, Lilja Lahtinen, Timothy Lopez, Shadi Jansouz, Aine Knott, Kara M Soroko and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports. Medicine, 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

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.

Linh LinInstitute of Molecular Medicine Finland (FIMM), Helsinki Institute of Life Sciences (HiLIFE) & Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.
Narges MoradiInstitute of Molecular Medicine Finland (FIMM), Helsinki Institute of Life Sciences (HiLIFE) & Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.
Iris A LähdeniemiInstitute of Molecular Medicine Finland (FIMM), Helsinki Institute of Life Sciences (HiLIFE) & Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.
Hanna K LaitinenInstitute of Molecular Medicine Finland (FIMM), Helsinki Institute of Life Sciences (HiLIFE) & Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.
Bassel AlsaedInstitute of Molecular Medicine Finland (FIMM), Helsinki Institute of Life Sciences (HiLIFE) & Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.
Lilja LahtinenInstitute of Molecular Medicine Finland (FIMM), Helsinki Institute of Life Sciences (HiLIFE) & Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.
Timothy LopezDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Shadi JansouzInstitute of Molecular Medicine Finland (FIMM), Helsinki Institute of Life Sciences (HiLIFE) & Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland.
Aine KnottDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Experimental Therapeutics Core and Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
Kara M SorokoDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Experimental Therapeutics Core and Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
Ilkka IloneniCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland; Department of General Thoracic and Esophageal Surgery, Heart and Lung Center, Helsinki University Hospital & University of Helsinki, Helsinki, Finland.
Prafulla C GokhaleDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Experimental Therapeutics Core and Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
Pasi A JänneDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA.
Heidi M HaikalaInstitute of Molecular Medicine Finland (FIMM), Helsinki Institute of Life Sciences (HiLIFE) & Translational Immunology Research Program (TRIMM), Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, Finland; iCAN Digital Precision Cancer Medicine Flagship, University of Helsinki, Helsinki, Finland; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Harvard Medical School, Boston, MA, USA; Center for Cancer Eradication Research, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Research Unit, Heart and Lung Center, Helsinki University Hospital, Helsinki, Finland. Electronic address: heidi.haikala@helsinki.fi.

Funding

Development of Combination Therapies to Delay/Prevent Acquired Drug ResistanceR35CA220497 · NCI · DANA-FARBER CANCER INST · PI JANNE, PASI A · 2018 to 2024
$7.2M
NCI NIH HHS R35 CA220497
6 · The paper itself

Abstract

Lung cancer, a leading cause of cancer-related mortality, is often driven by mutations in the key oncogenes epidermal growth factor receptor (EGFR) and Kirsten rat sarcoma virus (KRAS). Despite advancements of targeted therapies such as tyrosine kinase inhibitors, resistance remains a significant hurdle. Overexpression of HER3, associated with poor prognosis in non-small cell lung cancer (NSCLC), presents an alternative therapeutic target. In this study, we investigate the efficacy of the HER3-targeting antibody-drug conjugate HER3-DXd and its synergistic potential when combined with cell cycle and DNA damage response modulators. A significant synergy is observed with PARP inhibitors, effective in both EGFR- and KRAS-mutated NSCLC models. This combination markedly enhances DNA damage, induces apoptosis, and slows down in vivo tumor progression. Notably, this regimen also triggers antibody-dependent immunomodulatory effects through cGAS-STING pathway activation, potentiating innate immune cells for tumor killing. Our findings suggest that combining HER3-DXd with PARP inhibitors offers a promising therapeutic approach, effectively targeting diverse NSCLC subtypes.

Indexed as

Antineoplastic AgentsCarcinoma, Non-Small-Cell LungImmunoconjugatesLung NeoplasmsPoly(ADP-ribose) Polymerase InhibitorsReceptor, ErbB-3AnimalsApoptosisCell Line, TumorcGAS-STING Signaling PathwayDNA DamageDrug SynergismErbB ReceptorsFemaleHumansMembrane ProteinsAntineoplastic AgentsERBB3 protein, humanErbB ReceptorsImmunoconjugatesMembrane ProteinsPoly(ADP-ribose) Polymerase InhibitorsProto-Oncogene Proteins p21(ras)Receptor, ErbB-3STING Proteinantibody-dependent cellular cytotoxicityantibody-drug conjugateDNA damage responseEGFRepidermal growth factor receptorHER3innate immunityKirsten rat sarcoma virusKRASnon-small cell lung cancerNSCLCstimulator of interferon genes pathwaySTING pathway

Identifiers

PMID42628527
PMCPMC13589489

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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.