Evidence map›Paper›PMID 27533080›Full record

ArticleOncotarget2016

TP53 mutated glioblastoma stem-like cell cultures are sensitive to dual mTORC1/2 inhibition while resistance in TP53 wild type cultures can be overcome by combined inhibition of mTORC1/2 and Bcl-2.

Subramanian Venkatesan, Marlous Hoogstraat, Ester Caljouw, Tessa Pierson, Jochem K H Spoor, Lona Zeneyedpour, Hendrikus J Dubbink, Lennard J Dekker, Mariëlle van der Kaaij, Jenneke Kloezeman and 8 more

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

Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.4field-weighted citation impact, top 33% 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

5 citing papers in PubMed, 9 citations in OpenAlex.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Targeting mTOR for cancer therapy.Journal of hematology & oncology · 2019
    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

18 authors at 2 institutions in 1 country.

Subramanian VenkatesanDepartment of Neurosurgery, Brain Tumor Center Erasmus MC, Rotterdam, The Netherlands.
Marlous HoogstraatDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
Ester CaljouwPepscope BV, Utrecht, The Netherlands.
Tessa PiersonDepartment of Neurosurgery, Brain Tumor Center Erasmus MC, Rotterdam, The Netherlands.
Jochem K H SpoorDepartment of Neurosurgery, Brain Tumor Center Erasmus MC, Rotterdam, The Netherlands.
Lona ZeneyedpourDepartment of Neurology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Hendrikus J DubbinkDepartment of Pathology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Lennard J DekkerDepartment of Neurology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Mariëlle van der KaaijDepartment of Neurosurgery, Brain Tumor Center Erasmus MC, Rotterdam, The Netherlands.
Jenneke KloezemanDepartment of Neurosurgery, Brain Tumor Center Erasmus MC, Rotterdam, The Netherlands.
Lotte M E Berghauser PontDepartment of Neurosurgery, Brain Tumor Center Erasmus MC, Rotterdam, The Netherlands.
Nicolle J M BesselinkDepartment of Medical Oncology, University Medical Center Utrecht, Utrecht, The Netherlands.
Theo M LuiderDepartment of Neurology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Jos JoorePepscope BV, Utrecht, The Netherlands.
John W MartensDepartment of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Martine L M LamfersDepartment of Neurosurgery, Brain Tumor Center Erasmus MC, Rotterdam, The Netherlands.
Stefan SleijferCenter for Personalized Cancer Treatment (CPCT), University Medical Center Utrecht, Utrecht, The Netherlands.
Sieger LeenstraDepartment of Neurosurgery, Brain Tumor Center Erasmus MC, Rotterdam, The Netherlands.
Erasmus MC Cancer Institute · NLUniversity Medical Center Utrecht · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGlioblastoma is the most malignant tumor of the central nervous system and still lacks effective treatment. This study explores mutational biomarkers of 11 drugs targeting either the RTK/Ras/PI3K, the p53 or the Rb pathway using 25 patient-derived glioblastoma stem-like cell cultures (GSCs).

resultsWe found that TP53 mutated GSCs were approximately 3.5 fold more sensitive to dual inhibition of mammalian target of rapamycin complex 1 and 2 (mTORC1/2) compared to wild type GSCs. We identified that Bcl-2(Thr56/Ser70) phosphorylation contributed to the resistance of TP53 wild type GSCs against dual mTORC1/2 inhibition. The Bcl-2 inhibitor ABT-263 (navitoclax) increased sensitivity to the mTORC1/2 inhibitor AZD8055 in TP53 wild type GSCs, while sensitivity to AZD8055 in TP53 mutated GSCs remained unchanged.

conclusionOur data suggest that Bcl-2 confers resistance to mTORC1/2 inhibitors in TP53 wild type GSCs and that combined inhibition of both mTORC1/2 and Bcl-2 is worthwhile to explore further in TP53 wild type glioblastomas, whereas in TP53 mutated glioblastomas dual mTORC1/2 inhibitors should be explored.

Indexed as

Drug Resistance, NeoplasmAniline CompoundsBiomarkers, TumorBrain NeoplasmsCell Line, TumorCell SurvivalCohort StudiesDNA Mutational AnalysisDrug Screening Assays, AntitumorGlioblastomaHigh-Throughput Nucleotide SequencingHumansMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MorpholinesMutation(5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanolAniline CompoundsBCL2 protein, humanBiomarkers, TumorMechanistic Target of Rapamycin Complex 1Mechanistic Target of Rapamycin Complex 2MorpholinesMTOR protein, humannavitoclaxPhosphatidylinositol 3-KinasesProteomeProto-Oncogene Proteins c-bcl-2SulfonamidesTOR Serine-Threonine KinasesTP53 protein, humanTumor Suppressor Protein p53brain tumorgenetic biomarkerspersonalized medicineresistancesmall molecule kinase inhibitors

Identifiers

PMID27533080
PMCPMC5295441
OpenAlexW2516978199

What OpenQuestion holds

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LicenceCC BY
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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.