Evidence map›Paper›PMID 31842413›Full record

ArticleCancers2019

Implementing Patient-Derived Xenografts to Assess the Effectiveness of Cyclin-Dependent Kinase Inhibitors in Glioblastoma.

Janis J Noonan, Monika Jarzabek, Frank A Lincoln, Brenton L Cavanagh, Arhona R Pariag, Viktorija Juric, Leonie S Young, Keith L Ligon, Hanne Jahns, Daniella Zheleva and 4 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
0.8field-weighted citation impact, top 24% 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

12 citing papers in PubMed, 14 citations in OpenAlex.

  1. Review
  2. N-Glycoside of Indolo[2,3-Pharmaceuticals (Basel, Switzerland) · 2024
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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

14 authors at 5 institutions in 4 countries.

Janis J NoonanDepartment of Physiology & Medical Physics, Royal College of Surgeons in Ireland, D02 YN77 Dublin 2, Ireland.
Monika JarzabekDepartment of Physiology & Medical Physics, Royal College of Surgeons in Ireland, D02 YN77 Dublin 2, Ireland.ORCID 0000-0001-7008-4797
Frank A LincolnDepartment of Physiology & Medical Physics, Royal College of Surgeons in Ireland, D02 YN77 Dublin 2, Ireland.
Brenton L CavanaghCellular and Molecular Imaging Core, Royal College of Surgeons in Ireland, D02 YN77 Dublin 2, Ireland.ORCID 0000-0002-1582-5756
Arhona R PariagDepartment of Physiology & Medical Physics, Royal College of Surgeons in Ireland, D02 YN77 Dublin 2, Ireland.
Viktorija JuricDepartment of Physiology & Medical Physics, Royal College of Surgeons in Ireland, D02 YN77 Dublin 2, Ireland.
Leonie S YoungEndocrine Oncology Research Group, Department of Surgery, Royal College of Surgeons in Ireland, D02 YN77 Dublin 2, Ireland.
Keith L LigonDepartment of Oncologic Pathology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
Hanne JahnsPathobiology Section, School of Veterinary Medicine, University College Dublin, D02 YN77 Dublin 4, Ireland.ORCID 0000-0001-6944-154X
Daniella ZhelevaCyclacel Ltd., 1 James Lindsay Place, Dundee, Scotland DD1 5JJ, UK.
Jochen H M PrehnDepartment of Physiology & Medical Physics, Royal College of Surgeons in Ireland, D02 YN77 Dublin 2, Ireland.
Markus RehmInstitute of Cell Biology and Immunology, University of Stuttgart, D-70569 Stuttgart, Germany.
Annette T ByrneDepartment of Physiology & Medical Physics, Royal College of Surgeons in Ireland, D02 YN77 Dublin 2, Ireland.
Brona M MurphyDepartment of Physiology & Medical Physics, Royal College of Surgeons in Ireland, D02 YN77 Dublin 2, Ireland.
Royal College of Surgeons in Ireland · IECyclacel Pharmaceuticals (United Kingdom) · GBDana-Farber Cancer Institute · USUniversity College Dublin · IEUniversity of Stuttgart · DE

Funding

European Commission ITN Grant # 766069 GLIOTRAINHealth Research Board HRA_POR/2012/88
6 · The paper itself

Abstract

Glioblastoma (GBM) is the most common primary brain tumor with no available cure. As previously described, seliciclib, a first-generation cyclin-dependent kinase (CDK) inhibitor, down-regulates the anti-apoptotic protein, Mcl-1, in GBM, thereby sensitizing GBM cells to the apoptosis-inducing effects of the death receptor ligand, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Here, we have assessed the efficacy of seliciclib when delivered in combination with the antibody against human death receptor 5, drozitumab, in clinically relevant patient-derived xenograft (PDX) models of GBM. A reduction in viability and significant levels of apoptosis were observed in vitro in human GBM neurospheres following treatment with seliciclib plus drozitumab. While the co-treatment strategy induced a similar effect in PDX models, the dosing regimen required to observe seliciclib-targeted responses in the brain, resulted in lethal toxicity in 45% of animals. Additional studies showed that the second-generation CDK inhibitor, CYC065, with improved potency in comparison to seliciclib, induced a significant decrease in the size of human GBM neurospheres in vitro and was well tolerated in vivo, upon administration at clinically relevant doses. This study highlights the continued need for robust pre-clinical assessment of promising treatment approaches using clinically relevant models.

Indexed as

CDK inhibitorsCYC065drozitumabglioblastomaneurospherespatient-derived xenograftseliciclibTRAIL

Identifiers

PMID31842413
PMCPMC6966586
OpenAlexW2994894590

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.