Evidence map›Paper›PMID 32708903›Full record

ArticleCancers2020

TP5, a Peptide Inhibitor of Aberrant and Hyperactive CDK5/p25: A Novel Therapeutic Approach against Glioblastoma.

Emeline Tabouret, Herui Wang, Niranjana Amin, Jinkyu Jung, Romain Appay, Jing Cui, Qi Song, Antonio Cardone, Deric M Park, Mark R Gilbert and 2 more

Erratum issuedOpen access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cancers, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
0.7field-weighted citation impact, top 28% 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

10 citing papers in PubMed, 15 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. The role of Cdk5 in neurological disorders.Frontiers in cellular neuroscience · 2022
    Review
  8. Review
  9. Article
  10. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 5 institutions in 3 countries.

Emeline TabouretNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.ORCID 0000-0002-4031-2178
Herui WangNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Niranjana AminNeuronal Cytoskeletal Protein Regulation Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20824, USA.ORCID 0000-0001-9616-8294
Jinkyu JungNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Romain AppayTeam 8 GlioME, CNRS, INP, Inst Neurophysiopathol, Aix-Marseille University, 13005 Marseille, France.
Jing CuiNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Qi SongNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Antonio CardoneUniversity of Maryland Institute for Advanced Computer Studies, College Park, MD 20742, USA.
Deric M ParkDepartment of Neurology and the Committee on Clinical Pharmacology and Pharmacogenomics, The University of Chicago, Chicago, IL 60637, USA.
Mark R GilbertNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Harish PantNeuronal Cytoskeletal Protein Regulation Section, National Institute of Neurological Disorders and Stroke, Bethesda, MD 20824, USA.
Zhengping ZhuangNeuro-Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
National Institutes of Health · USCentre National de la Recherche Scientifique · FRNational Institute of Neurological Disorders and Stroke · USResearch Institute for Advanced Computer Science · USUniversity of Chicago · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

We examined the efficacy of selective inhibition of cyclin-dependent kinase 5 (CDK5) in glioblastoma by TP5. We analyzed its impact in vitro on CDK5 expression and activity, cell survival, apoptosis and cell cycle. DNA damage was analyzed using the expression of γH2A.X and phosphorylated ATM. Its tolerance and efficacy were assessed on in vivo xenograft mouse models. We showed that TP5 decreased the activity but not the expression of CDK5 and p35. TP5 alone impaired cell viability and colony formation of glioblastoma cell lines and induced apoptosis. TP5 increased DNA damage by inhibiting the phosphorylation of ATM, leading to G1 arrest. Whereas CDK5 activity is increased by DNA-damaging agents such as temozolomide and irradiation, TP5 was synergistic with either temozolomide or irradiation due to an accumulation of DNA damage. Concomitant use of TP5 and either temozolomide or irradiation reduced the phosphorylation of ATM, increased DNA damage, and inhibited the G2/M arrest induced by temozolomide or irradiation. TP5 alone suppressed the tumor growth of orthotopic glioblastoma mouse model. The treatment was well tolerated. Finally, alone or in association with irradiation or temozolomide, TP5 prolonged mouse survival. TP5 alone or in association with temozolomide and radiotherapy is a promising therapeutic option for glioblastoma.

Indexed as

ATMCDK5chemotherapyDNA damageglioblastomaradiotherapytargeted therapy

Identifiers

PMID32708903
PMCPMC7409269
OpenAlexW3042252937

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.