Evidence map›Paper›PMID 33686114›Full record

ArticleScientific reports2021

Pre-therapeutic efficacy of the CDK inhibitor dinaciclib in medulloblastoma cells.

Marta Buzzetti, Sonia Morlando, Dimitrios Solomos, Ammara Mehmood, Alexander W I Cox, Mattia Chiesa, Yuri D'Alessandra, Michela Garofalo, Caroline H Topham, Gianpiero Di Leva

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. 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 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.3field-weighted citation impact, top 9% 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

14 citing papers in PubMed, 20 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Medulloblastoma in the Modern Era: Review of Contemporary Trials, Molecular Advances, and Updates in Management.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022
    Review
  12. Review
  13. Article
  14. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 5 institutions in 2 countries.

Marta Buzzetti *School of Science, Engineering and Environment, Biomedical Research Centre, Salford, Greater Manchester, UK.
Sonia Morlando *School of Science, Engineering and Environment, Biomedical Research Centre, Salford, Greater Manchester, UK.
Dimitrios SolomosSchool of Science, Engineering and Environment, Biomedical Research Centre, Salford, Greater Manchester, UK.
Ammara MehmoodSchool of Science, Engineering and Environment, Biomedical Research Centre, Salford, Greater Manchester, UK.
Alexander W I CoxCancer Research UK Lung Cancer Centre of Excellence, at Manchester and University College London, London, UK.
Mattia ChiesaBioinformatics and Artificial Intelligence Facility, Centro Cardiologico Monzino IRCCS, Milan, Italy.
Yuri D'AlessandraImmunology and Functional Genomics Unit, Centro Cardiologico Monzino IRCCS, Milan, Italy.
Michela GarofaloTranscriptional Networks in Lung Cancer Group, Cancer Research UK Manchester Institute, University of Manchester, Manchester, UK.
Caroline H TophamSchool of Science, Engineering and Environment, Biomedical Research Centre, Salford, Greater Manchester, UK.
Gianpiero Di LevaSchool of Pharmacy and Bioengineering, Guy Hilton Research Centre, Keele University, Stoke-on-Trent, UK. g.dileva@keele.ac.uk.
Centro Cardiologico Monzino · ITCancer Research UK Manchester Institute · GBKeele University · GBUniversity College London · GBUniversity of Manchester · GB

Funding

Kidscan UK PhD studentshipKidscan UK Startup GrantKidscan UK Student Placement Award
6 · The paper itself

Abstract

Medulloblastoma (MB) is the most common aggressive paediatric brain tumour and, despite the recent progress in the treatments of MB patients, there is still an urgent need of complementary or alternative therapeutic options for MB infants. Cyclin Dependent Kinase inhibitors (CDKi) are at the front-line of novel targeted treatments for multiple cancers and the CDK4/6 specific inhibitor palbociclib has been pre-clinically identified as an effective option for MB cells. Herein, we identified the pan-CDKi dinaciclib as a promising alternative to palbociclib for the suppression of MB cells proliferation. We present evidence supporting dinaciclib's ability to inhibit MB cells in vitro proliferation at considerably lower doses than palbociclib. Sequencing data and pathway analysis suggested that dinaciclib is a potent cell death inducer in MB cells. We found that dinaciclib-triggered apoptosis is triggered by CDK9 inhibition and the resultant reduction in RNA pol II phosphorylation, which leads to the downregulation of the oncogenic marker MYC, and the anti-apoptotic protein MCL-1. Specifically, we demonstrated that MCL-1 is a key apoptotic mediator for MB cells and co-treatment of dinaciclib with BH3 mimetics boosts the therapeutic efficacy of dinaciclib. Together, these findings highlight the potential of multi-CDK inhibition by dinaciclib as an alternative option to CDK4/6 specific inhibition, frequently associated with drug resistance in patients.

Indexed as

Cyclin-Dependent KinasesMedulloblastomaNeoplasm ProteinsCell ProliferationCyclic N-OxidesDrug Screening Assays, AntitumorHumansIndolizinesProtein Kinase InhibitorsPyridinium CompoundsCyclic N-OxidesCyclin-Dependent KinasesdinaciclibIndolizinesNeoplasm ProteinsProtein Kinase InhibitorsPyridinium Compounds

Identifiers

PMID33686114
PMCPMC7940474
OpenAlexW3133777844

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.