Evidence map›Paper›PMID 28915653›Full record

ArticleOncotarget2017

Dual targeting of MDM2 and BCL2 as a therapeutic strategy in neuroblastoma.

Alan Van Goethem, Nurten Yigit, Myrthala Moreno-Smith, Sanjeev A Vasudevan, Eveline Barbieri, Frank Speleman, Jason Shohet, Jo Vandesompele, Tom Van Maerken

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

Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.1field-weighted citation impact, top 13% 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

15 citing papers in PubMed, 33 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Review
  5. Article
  6. Advancing therapy for neuroblastoma.Nature reviews. Clinical oncology · 2022
    Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Molecularly Targeted Therapy for Neuroblastoma.Children (Basel, Switzerland) · 2018
    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 at 5 institutions in 2 countries.

Alan Van GoethemCenter for Medical Genetics Ghent (CMGG), Ghent University, Ghent, Belgium.
Nurten YigitCenter for Medical Genetics Ghent (CMGG), Ghent University, Ghent, Belgium.
Myrthala Moreno-SmithDepartment of Pediatrics, Section of Hematology-Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
Sanjeev A VasudevanDepartment of Pediatrics, Section of Hematology-Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
Eveline BarbieriDepartment of Pediatrics, Section of Hematology-Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
Frank SpelemanCenter for Medical Genetics Ghent (CMGG), Ghent University, Ghent, Belgium.
Jason ShohetDepartment of Pediatrics, Section of Hematology-Oncology, Texas Children's Cancer Center, Baylor College of Medicine, Houston, Texas, USA.
Jo VandesompeleCenter for Medical Genetics Ghent (CMGG), Ghent University, Ghent, Belgium.
Tom Van MaerkenCenter for Medical Genetics Ghent (CMGG), Ghent University, Ghent, Belgium.
Ghent University Hospital · BEBaylor College of Medicine · USChildren's Cancer Center · USCancer Research Institute Ghent · BEGhent University · BE

Funding

Targeting the G-CSF/STAT3 signaling pathway in neuroblastoma cancer stem cellsR01CA174808 · NCI · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI SHOHET, JASON M · 2014 to 2018
$1.7M
NCI NIH HHS R01 CA174808
6 · The paper itself

Abstract

Wild-type p53 tumor suppressor activity in neuroblastoma tumors is hampered by increased MDM2 activity, making selective MDM2 antagonists an attractive therapeutic strategy for this childhood malignancy. Since monotherapy in cancer is generally not providing long-lasting clinical responses, we here aimed to identify small molecule drugs that synergize with idasanutlin (RG7388). To this purpose we evaluated 15 targeted drugs in combination with idasanutlin in three p53 wild type neuroblastoma cell lines and identified the BCL2 inhibitor venetoclax (ABT-199) as a promising interaction partner. The venetoclax/idasanutlin combination was consistently found to be highly synergistic in a diverse panel of neuroblastoma cell lines, including cells with high MCL1 expression levels. A more pronounced induction of apoptosis was found to underlie the synergistic interaction, as evidenced by caspase-3/7 and cleaved PARP measurements. Mice carrying orthotopic xenografts of neuroblastoma cells treated with both idasanutlin and venetoclax had drastically lower tumor weights than mice treated with either treatment alone. In conclusion, these data strongly support the further evaluation of dual BCL2/MDM2 targeting as a therapeutic strategy in neuroblastoma.

Indexed as

idasanutlinneuroblastomap53synergismvenetoclax

Identifiers

PMID28915653
PMCPMC5593624
OpenAlexW2726242674

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.