Evidence map›Paper›PMID 33994371›Full record

ArticleClinical cancer research : an official journal of the American Association for Cancer Research2021

Dual Targeting of Chromatin Stability By The Curaxin CBL0137 and Histone Deacetylase Inhibitor Panobinostat Shows Significant Preclinical Efficacy in Neuroblastoma.

Lin Xiao, Klaartje Somers, Jayne Murray, Ruby Pandher, Mawar Karsa, Emma Ronca, Angelika Bongers, Rachael Terry, Anahid Ehteda, Laura D Gamble and 28 more

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

Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
2.8field-weighted citation impact, top 7% 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

16 citing papers in PubMed, 30 citations in OpenAlex.

  1. The cell-permeable iron chelator M606 inhibits MYCN-driven neuroblastoma via an E2F3-mediated response.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. 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

38 authors at 7 institutions in 2 countries.

Lin Xiao *Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Klaartje Somers *Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.ORCID 0000-0002-7644-4121
Jayne MurrayChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.ORCID 0000-0002-1861-6570
Ruby PandherChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Mawar KarsaChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Emma RoncaChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Angelika BongersChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Rachael TerryChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.ORCID 0000-0002-6260-7372
Anahid EhtedaChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.ORCID 0000-0002-4118-1499
Laura D GambleChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.ORCID 0000-0001-8496-9705
Natalia IssaevaDepartment of Otolaryngology/Head and Neck Surgery, Department of Pathology and Lab Medicine, Lineberger Comprehensive Cancer Center, UNC-Chapel Hill, Chapel Hill, North Carolina.
Katerina I LeonovaDepartment of Cell Stress Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York.ORCID 0000-0001-5068-5341
Aisling O'ConnorChildren's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.
Chelsea MayohChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.ORCID 0000-0002-6398-3046
Pooja VenkatChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.ORCID 0000-0002-9171-7562
Hazel QuekMental Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.ORCID 0000-0001-5597-5372
Jennifer BrandChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Frances K KusumaChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Jessica A PettittChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Erin MosmannChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Adam KearnsChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Georgina EdenChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Stephanie AlfredChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Sophie AllanChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Lei ZhaiChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Alvin KamiliChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Andrew J GiffordChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.ORCID 0000-0002-4092-2347
Daniel R CarterChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Michelle J HendersonChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.ORCID 0000-0003-2741-3852
Jamie I FletcherChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.ORCID 0000-0003-2949-9469
Glenn MarshallChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Ricky W JohnstoneImmune Defence Laboratory, Cancer Immunology Program, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.
Anthony J CesareChildren's Medical Research Institute, University of Sydney, Westmead, New South Wales, Australia.ORCID 0000-0002-0864-1254
David S ZieglerChildren's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia.
Andrei V GudkovDepartment of Cell Stress Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York.
Katerina V GurovaDepartment of Cell Stress Biology, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, New York.
Murray D Norris *Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia. mhaber@ccia.unsw.edu.au mnorris@ccia.unsw.edu.au.ORCID 0000-0002-0632-4589
Michelle Haber *Children's Cancer Institute, Lowy Cancer Research Centre, University of New South Wales Sydney, New South Wales, Australia. mhaber@ccia.unsw.edu.au mnorris@ccia.unsw.edu.au.ORCID 0000-0003-2036-8817
Cancer Institute of New South Wales · AURoswell Park Comprehensive Cancer Center · USChildren's Medical Research Institute · AUPeter MacCallum Cancer Centre · AUQIMR Berghofer Medical Research Institute · AUUniversity of North Carolina Health Care · USUniversity of Technology Sydney · AU

Funding

Modulation of cancer specific transcriptional factors with small moleculesR01CA197967 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI GUROVA, KATERINA V · 2015 to 2019
$2.0M
NCI NIH HHS R01 CA197967
6 · The paper itself

Abstract

purposeWe investigated whether targeting chromatin stability through a combination of the curaxin CBL0137 with the histone deacetylase (HDAC) inhibitor, panobinostat, constitutes an effective multimodal treatment for high-risk neuroblastoma. EXPERIMENTAL

designThe effects of the drug combination on cancer growth were examined

resultsThe combination of CBL0137 and panobinostat enhanced nucleosome destabilization, induced an IFN response, inhibited DNA damage repair, and synergistically suppressed cancer cell growth. Similar synergistic effects were observed when combining CBL0137 with other HDAC inhibitors. The CBL0137/panobinostat combination significantly delayed cancer progression in xenograft models of poor outcome high-risk neuroblastoma. Complete tumor regression was achieved in the transgenic Th-MYCN neuroblastoma model which was accompanied by induction of a type I IFN and immune response. Tumor transplantation experiments further confirmed that the presence of a competent adaptive immune system component allowed the exploitation of the full potential of the drug combination.

conclusionsThe combination of CBL0137 and panobinostat is effective and well-tolerated in preclinical models of aggressive high-risk neuroblastoma, warranting further preclinical and clinical investigation in other pediatric cancers. On the basis of its potential to boost IFN and immune responses in cancer models, the drug combination holds promising potential for addition to immunotherapies.

Indexed as

AnimalsCarbazolesChromatinDrug CombinationsDrug Evaluation, PreclinicalHistone Deacetylase InhibitorsMiceNeuroblastomaPanobinostatTumor Cells, CulturedCarbazolesCBLC137ChromatinDrug CombinationsHistone Deacetylase InhibitorsPanobinostat

Identifiers

PMID33994371
PMCPMC8380471
OpenAlexW3160674257

What OpenQuestion holds

Textmetadata
LicenceTDM
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.