Evidence map›Paper›PMID 39542886›Full record

ArticleJournal of cancer research and clinical oncology2024

A novel mouse model recapitulating the MMR-defective SCLC subtype uncovers an actionable sensitivity to immune checkpoint blockade.

Olta Ibruli, France Rose, Filippo Beleggia, Anna Schmitt, Maria Cartolano, Lucia Torres Fernandez, Julia Saggau, Debora Bonasera, Martha Kiljan, Gokcen Gozum and 15 more

Abstract read
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In one paragraph

Article in Journal of cancer research and clinical oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
  4. Article
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

25 authors.

Olta Ibruli *Department of Translational Genomics, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
France Rose *Center for Molecular Medicine Cologne, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Filippo BeleggiaDepartment of Translational Genomics, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Anna SchmittDepartment I of Internal Medicine, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Maria CartolanoDepartment of Translational Genomics, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Lucia Torres FernandezDepartment of Translational Genomics, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Julia SaggauCenter for Molecular Medicine Cologne, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Debora BonaseraCenter for Molecular Medicine Cologne, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Martha KiljanDepartment I of Internal Medicine, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Gokcen GozumDepartment I of Internal Medicine, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Luca LichiusDepartment II of Internal Medicine, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Jiali CaiCenter for Molecular Medicine Cologne, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Li-Na NiuCenter for Molecular Medicine Cologne, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Manoela Iannicelli CaiaffaDepartment of Translational Genomics, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Jan M HerterCenter for Molecular Medicine Cologne, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Henning WalczakInstitute of Biochemistry I, Center for Biochemistry, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Gianmaria LiccardiCenter for Molecular Medicine Cologne, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Holger GrüllInstitute for Diagnostic and Interventional Radiology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Reinhard BüttnerInstitute of Pathology, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Graziella BoscoDepartment of Translational Genomics, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Julie GeorgeDepartment of Translational Genomics, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Roman K ThomasDepartment of Translational Genomics, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Kasia Bozek *Center for Molecular Medicine Cologne, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Hans Christian Reinhardt *Department of Hematology and Stem Cell Transplantation, University Hospital Essen, Essen, Germany.
Grit S Herter-Sprie *Department I of Internal Medicine, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany. grit.herter-sprie@fachklinik-hornheide.de.

Funding

Alexander von Humboldt-Stiftung 214342/Z/18/ZCancer Research UK Programme A27323CANcer TARgeting (CANTAR) NW21-062ACenter for Biochemistry, Univeristy of Cologne 956400Center for Molecular Medicine Cologne, University of Cologne CAP-13Center for Molecular Medicine Cologne, University of Cologne CAP-16Deutsche Forschungsgemeinschaft (SFB1399) 413326622Deutsche Forschungsgemeinschaft(SFB1430) 424228829Deutsche Forschungsgemeinschaft(SFB1530) 455784452Deutsche Krebshilfe 1117240Else Kröner-Fresenius-Stiftung EKFS-2014-A06German Ministry of Education and Research 01ZX1901Medical Research Council MR/S00811X/1Mildred Scheel Nachwuchszentrum 70113307
6 · The paper itself

Abstract

purposeSmall cell lung cancer (SCLC) has an extremely poor prognosis. Despite high initial response rates to chemotherapy and modest survival improvements with the addition of immune checkpoint inhibitors (ICI), almost all patients experience relapse and fatal outcomes. Recent genomic insights uncovered extensive molecular heterogeneity in addition to the almost uniform loss of RB1 and TRP53. Additionally, defective DNA mismatch repair (MMR) has recently been described in some SCLC cases. Here, we generated a novel SCLC mouse model capturing MMR deficiency and assessed immunotherapy responses.

methodsWe developed an MMR-deficient genetically engineered mouse model (GEMM) of SCLC by introducing a conditional Msh2 gene, crucial for maintaining MMR integrity, into the standard Rb1

resultsMMR-defective SCLC tumors (Rb1

conclusionWe propose a novel RPM mouse model as a suitable system to mimic MMR-defective SCLC and tumors with high TMB. We provide in vivo evidence that Msh2 deficiency enhances ICI sensitivity. These findings could contribute to stratifying SCLC patients to immunotherapy, thereby improving treatment outcomes.

Indexed as

Disease Models, AnimalDNA Mismatch RepairImmune Checkpoint InhibitorsLung NeoplasmsMutS Homolog 2 ProteinSmall Cell Lung CarcinomaAnimalsHumansMiceTumor Suppressor Protein p53Immune Checkpoint InhibitorsMsh2 protein, mouseMutS Homolog 2 ProteinTumor Suppressor Protein p53Genetically engineered mouse modelImmune checkpoint inhibitorMismatch repair deficiencySmall cell lung cancerTumor mutational burden

Identifiers

PMID39542886
PMCPMC11564195

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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.