Evidence map›Paper›PMID 35603902›Full record

ReviewInternational journal of cancer2022

Changing paradigms in oncology: Toward noncytotoxic treatments for advanced gliomas.

Nikolaus von Knebel Doeberitz, Daniel Paech, Dominik Sturm, Stefan Pusch, Sevin Turcan, Yogen Saunthararajah

Open access · bronzeAbstract readReview
In one paragraph

Review in International journal of cancer, 2022. 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
1.5field-weighted citation impact, top 17% 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, 11 citations in OpenAlex.

  1. Article
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  5. Review
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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

6 authors at 3 institutions in 2 countries.

Nikolaus von Knebel DoeberitzDivision of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.ORCID 0000-0002-8453-3220
Daniel PaechDivision of Radiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Dominik SturmHopp Children's Cancer Center (KiTZ) Heidelberg, Heidelberg, Germany.
Stefan PuschDepartment of Neuropathology, Institute of Pathology, Ruprecht-Karls-University Heidelberg, Heidelberg, Germany.
Sevin TurcanDepartment of Neurology, Heidelberg University Hospital, Heidelberg, Germany.
Yogen SaunthararajahDepartment of Translational Hematology and Oncology Research, Taussig Cancer Institute, Cleveland Clinic, Cleveland, Ohio, USA.ORCID 0000-0002-9757-1031
German Cancer Research Center · DECleveland Clinic · USHeidelberg University · DE

Funding

TUMOR METABOLISM PROGRAMP30CA043703 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI Amar Desai · 1987 to 2026
$142.3M
Targeting Enzymatic Regulation of Fetal Hemoglobin RepressionP01HL146372 · NHLBI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI SAUNTHARARAJAH, YOGEN · 2019 to 2023
$10.9M
Imaging Liver Cancer ProliferationR01CA204373 · NCI · CASE WESTERN RESERVE UNIVERSITY · PI LEE, ZHENGHONG, SAUNTHARARAJAH, YOGEN · 2016 to 2021
$1.8M
A Novel, Non-Cytotoxic, Epigenetic Therapeutic for Sickle Cell DiseaseR44HL135896 · NHLBI · DENOVOTHERAPIES, LLC · PI DESIMONE, JOSEPH, SAUNTHARARAJAH, YOGEN · 2017 to 2019
$1.7M
Optimizing decitabine regimen + formulation for nonDNA damaging DNMT1 depletionR01CA138858 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI SAUNTHARARAJAH, YOGEN · 2009 to 2013
$1.6M
Operationalizing DNMT1-Targeting to Treat Chemorefractory Pancreatic CancerR21CA263430 · NCI · CLEVELAND CLINIC LERNER COM-CWRU · PI SAUNTHARARAJAH, YOGEN · 2022 to 2023
$409k
NCI NIH HHS P30 CA043703NCI NIH HHS R01 CA138858NCI NIH HHS R01 CA204373NCI NIH HHS R21 CA263430NHLBI NIH HHS P01 HL146372NHLBI NIH HHS R44 HL135896
6 · The paper itself

Abstract

Glial-lineage malignancies (gliomas) recurrently mutate and/or delete the master regulators of apoptosis p53 and/or p16/CDKN2A, undermining apoptosis-intending (cytotoxic) treatments. By contrast to disrupted p53/p16, glioma cells are live-wired with the master transcription factor circuits that specify and drive glial lineage fates: these transcription factors activate early-glial and replication programs as expected, but fail in their other usual function of forcing onward glial lineage-maturation-late-glial genes have constitutively "closed" chromatin requiring chromatin-remodeling for activation-glioma-genesis disrupts several epigenetic components needed to perform this work, and simultaneously amplifies repressing epigenetic machinery instead. Pharmacologic inhibition of repressing epigenetic enzymes thus allows activation of late-glial genes and terminates glioma self-replication (self-replication = replication without lineage-maturation), independent of p53/p16/apoptosis. Lineage-specifying master transcription factors therefore contrast with p53/p16 in being enriched in self-replicating glioma cells, reveal a cause-effect relationship between aberrant epigenetic repression of late-lineage programs and malignant self-replication, and point to specific epigenetic targets for noncytotoxic glioma-therapy.

Indexed as

Brain NeoplasmsGliomaChromatinCyclin-Dependent Kinase Inhibitor p16HumansTranscription FactorsTumor Suppressor Protein p53ChromatinCyclin-Dependent Kinase Inhibitor p16Transcription FactorsTumor Suppressor Protein p53cancer epigeneticsepigeneticgliomaglioma therapyneurooncology

Identifiers

PMID35603902
PMCPMC9474618
OpenAlexW4281290089

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.