Evidence map›Paper›PMID 38662542›Full record

ArticleCell reports2024

The MYCN 5' UTR as a therapeutic target in neuroblastoma.

Marina P Volegova, Lauren E Brown, Ushashi Banerjee, Ruben Dries, Bandana Sharma, Alyssa Kennedy, John A Porco, Rani E George

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

6 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Article
  3. A Dimeric Rocaglate Promotes Multivalent eIF4A-RNA Assembly.bioRxiv : the preprint server for biology · 2026
    Article
  4. Article
  5. Review
  6. 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

8 authors at 4 institutions in 1 country.

Marina P VolegovaDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Lauren E BrownBoston University, Center for Molecular Discovery (BU-CMD), Boston, MA, USA; Boston University, Department of Chemistry, Boston, MA, USA.
Ushashi BanerjeeDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
Ruben DriesBoston University School of Medicine, Computational Biomedicine, Boston, MA, USA.
Bandana SharmaDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Alyssa KennedyBoston Children's Cancer and Blood Disorders Center, Pediatric Hematology/Oncology, Boston, MA, USA.
John A PorcoBoston University, Center for Molecular Discovery (BU-CMD), Boston, MA, USA; Boston University, Department of Chemistry, Boston, MA, USA.
Rani E GeorgeDepartment of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pediatrics, Harvard Medical School, Boston, MA, USA. Electronic address: rani_george@dfci.harvard.edu.
Boston University · USHarvard University · USDana-Farber/Boston Children's Cancer and Blood Disorders Center · USDana-Farber Cancer Institute · US

Funding

Chemical Synthesis of Complex Natural Products for Translational ScienceR35GM118173 · NIGMS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI JOHN A. PORCO · 2016 to 2026
$8.2M
BU-CMD Chemical Library Consortium: Fostering Collaborations between Chemists and Biologists for Translational DiscoveryU01TR002625 · NCATS · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · PI PORCO, JOHN A. · 2020 to 2023
$2.7M
Translation initiation as a therapeutic target in neuroblastomaR21CA267521 · NCI · DANA-FARBER CANCER INST · PI GEORGE, RANI E. · 2023 to 2024
$454k
NCATS NIH HHS U01 TR002625NCI NIH HHS R21 CA267521NIGMS NIH HHS R35 GM118173
6 · The paper itself

Abstract

Tumor MYCN amplification is seen in high-risk neuroblastoma, yet direct targeting of this oncogenic transcription factor has been challenging. Here, we take advantage of the dependence of MYCN-amplified neuroblastoma cells on increased protein synthesis to inhibit the activity of eukaryotic translation initiation factor 4A1 (eIF4A1) using an amidino-rocaglate, CMLD012824. Consistent with the role of this RNA helicase in resolving structural barriers in 5' untranslated regions (UTRs), CMLD012824 increased eIF4A1 affinity for polypurine-rich 5' UTRs, including that of the MYCN and associated transcripts with critical roles in cell proliferation. CMLD012824-mediated clamping of eIF4A1 spanned the full lengths of mRNAs, while translational inhibition was mediated through 5' UTR binding in a cap-dependent and -independent manner. Finally, CMLD012824 led to growth inhibition in MYCN-amplified neuroblastoma models without generalized toxicity. Our studies highlight the key role of eIF4A1 in MYCN-amplified neuroblastoma and demonstrate the therapeutic potential of disrupting its function.

Indexed as

5' Untranslated RegionsEukaryotic Initiation Factor-4ANeuroblastomaN-Myc Proto-Oncogene ProteinAnimalsCell Line, TumorCell ProliferationFemaleHumansMiceMice, Inbred C57BLRNA, Messenger5' Untranslated RegionsEIF4A1 protein, humanEukaryotic Initiation Factor-4AMYCN protein, humanN-Myc Proto-Oncogene ProteinRNA, Messengeramidino-rocaglateCP: CancerCP: Molecular biologyeIF4A1MYCNMYCN amplificationneuroblastomaPAR-CLIPribosome profilingrocaglatetranslationtranslation regulation

Identifiers

PMID38662542
PMCPMC11284644
OpenAlexW4395063652

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.