Evidence map›Paper›PMID 36323843›Full record

ArticleNPJ precision oncology2022

Cytidine analogs are synthetic lethal with base excision repair default due to MBD4 deficiency.

Thomas Chabot, Fariba Nemati, Aurélie Herbette, Alexandre Demeyer, Stéphane Dayot, Olivier Ganier, Samar Alsafadi, Sophie Gardrat, Pascale Mariani, Marie Luporsi and 9 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in NPJ precision oncology, 2022. 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
0.2field-weighted citation impact, top 54% 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

4 citing papers in PubMed, 3 citations in OpenAlex.

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

19 authors at 3 institutions in 1 country.

Thomas ChabotInserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe labellisée par la Ligue Nationale Contre le Cancer, Institut Curie, PSL Research University, Paris, 75005, France.
Fariba NematiLaboratory of Preclinical Investigation, Translational Research Department, Institut Curie, PSL Research University, Paris, 75005, France.
Aurélie HerbetteBiophenics, PICT-IBiSa, Translational Research Department, Institut Curie, PSL Research University, Paris, France.
Alexandre DemeyerInserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe labellisée par la Ligue Nationale Contre le Cancer, Institut Curie, PSL Research University, Paris, 75005, France.
Stéphane DayotInserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe labellisée par la Ligue Nationale Contre le Cancer, Institut Curie, PSL Research University, Paris, 75005, France.
Olivier GanierInserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe labellisée par la Ligue Nationale Contre le Cancer, Institut Curie, PSL Research University, Paris, 75005, France.
Samar AlsafadiUveal Melanoma Group, Translational Research Department, Institut Curie, PSL Research University, Paris, 75005, France.
Sophie GardratDepartment of Biopathology, Institut Curie, PSL Research University, Paris, 75005, France.
Pascale MarianiDepartment of surgical oncology, Institut Curie, PSL Research University, Paris, 75005, France.
Marie LuporsiDepartment of Nuclear Medicine, Institut Curie, PSL Research University, Paris, 75005, France.ORCID http://orcid.org/0000-0001-7891-7642
Maxime CorbéBiophenics, PICT-IBiSa, Translational Research Department, Institut Curie, PSL Research University, Paris, France.ORCID http://orcid.org/0000-0002-9495-2832
Vincent ServoisDepartment of Medical Imaging, Institut Curie, PSL Research University, Paris, 75005, France.ORCID http://orcid.org/0000-0002-8378-8432
Nathalie CassouxDepartment of Ocular Oncology, Institut Curie, Paris, 75005, France.
Didier DecaudinLaboratory of Preclinical Investigation, Translational Research Department, Institut Curie, PSL Research University, Paris, 75005, France.
Sergio Roman RomanLaboratory of Preclinical Investigation, Translational Research Department, Institut Curie, PSL Research University, Paris, 75005, France.
Elaine Del NeryBiophenics, PICT-IBiSa, Translational Research Department, Institut Curie, PSL Research University, Paris, France.
Sophie Piperno-NeumannDepartment of Medical Oncology, Institut Curie, PSL Research University, Paris, 75005, France.
Marc-Henri SternInserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe labellisée par la Ligue Nationale Contre le Cancer, Institut Curie, PSL Research University, Paris, 75005, France.ORCID http://orcid.org/0000-0002-8100-2272
Manuel RodriguesInserm U830, DNA Repair and Uveal Melanoma (D.R.U.M.), Equipe labellisée par la Ligue Nationale Contre le Cancer, Institut Curie, PSL Research University, Paris, 75005, France. manuel.rodrigues@curie.fr.ORCID http://orcid.org/0000-0002-5443-0802
Université Paris Sciences et Lettres · FRInserm · FRDélégation Paris 5 · FR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Inactivating mutations of MBD4 have been reported in subsets of various tumors. A deficiency of this DNA glycosylase, recognizing specifically T:G mismatch resulting from the deamination of methyl-cytosine, results in a hypermutated phenotype due to the accumulation of CpG>TpG transitions. Here, we hypothesize that the difference in DNA metabolism consecutive to MBD4 deficiency may result in specific cytotoxicities in MBD4-deficient tumor cells in a synthetic lethality fashion. After a large-scale drug repurposing screen, we show in two isogenic MBD4 knock-out cell models that the inactivation of MBD4 sensitizes cancer cells to cytidine analogs. We further confirm the exquisite activity of gemcitabine in an MBD4-deficient co-clinical model as (i) it completely prevented the development of an MBD4-deficient uveal melanoma patient-derived xenograft and (ii) treatment in the corresponding patient resulted in an exceptional tumor response. These data suggest that patients harboring MBD4-deficient tumors may be treated efficiently by cytidine analogs.

Identifiers

PMID36323843
PMCPMC9630501
OpenAlexW4308057445

What OpenQuestion holds

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Registered trials

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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.