Evidence map›Paper›PMID 39222276›Full record

ArticleApoptosis : an international journal on programmed cell death2024

BH3-mimetics or DNA-damaging agents in combination with RG7388 overcome p53 mutation-induced resistance to MDM2 inhibition.

N V Pervushin, D K Nilov, S V Pushkarev, V O Shipunova, A S Badlaeva, M A Yapryntseva, D V Kopytova, B Zhivotovsky, G S Kopeina

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Article in Apoptosis : an international journal on programmed cell death, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. 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

9 authors.

N V PervushinEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.
D K NilovBelozersky Institute of Physicochemical Biology, Lomonosov Moscow State University, Moscow, 119991, Russia.
S V PushkarevFaculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, Moscow, 119234, Russia.
V O ShipunovaShemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, 117997, Russia.
A S BadlaevaKulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Russian Ministry of Health, Moscow, 117513, Russia.
M A YapryntsevaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.
D V KopytovaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia.
B ZhivotovskyEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia. Boris.Zhivotovsky@ki.se.
G S KopeinaEngelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, 119991, Russia. lirroster@gmail.com.

Funding

Cancerfonden 222013Cancerföreningen i Stockholm 181301The Russian Science Foundation 23-74-30006
6 · The paper itself

Abstract

The development of drug resistance reduces the efficacy of cancer therapy. Tumor cells can acquire resistance to MDM2 inhibitors, which are currently under clinical evaluation. We generated RG7388-resistant neuroblastoma cells, which became more proliferative and metabolically active and were less sensitive to DNA-damaging agents in vitro and in vivo, compared with wild-type cells. The resistance was associated with a mutation of the p53 protein (His193Arg). This mutation abated its transcriptional activity via destabilization of the tetrameric p53-DNA complex and was observed in many cancer types. Finally, we found that Cisplatin and various BH3-mimetics could enhance RG7388-mediated apoptosis in RG7388-resistant neuroblastoma cells, thereby partially overcoming resistance to MDM2 inhibition.

Indexed as

ApoptosisDrug Resistance, NeoplasmMutationProto-Oncogene Proteins c-mdm2Tumor Suppressor Protein p53AnimalsAntineoplastic AgentsCell Line, TumorCisplatinDNA DamageHumansMiceNeuroblastomapara-AminobenzoatesPyrrolidinesAntineoplastic AgentsCisplatinMDM2 protein, humanpara-AminobenzoatesProto-Oncogene Proteins c-mdm2PyrrolidinesRG7388Tumor Suppressor Protein p53BH3-mimeticsDrug resistanceMDM2p53 mutationRG7388

Identifiers

PMID39222276
PMCPMC11550243

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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.