Evidence map›Paper›PMID 26686971›Full record

Trial reportMolecular oncology2016

Novel pharmacodynamic biomarkers for MYCN protein and PI3K/AKT/mTOR pathway signaling in children with neuroblastoma.

Jennifer R Smith, Lucas Moreno, Simon P Heaton, Louis Chesler, Andrew D J Pearson, Michelle D Garrett

Open access · bronzeAbstract readClinical Trial
In one paragraph

Trial report in Molecular oncology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

13 citing papers in PubMed, 21 citations in OpenAlex.

  1. Trial
  2. Article
  3. Review
  4. Anti-tumor effect of Huaier extract against neuroblastoma cellsInternational journal of medical sciences · 2021
    Article
  5. Scientific reports · 2020
    Article
  6. Review
  7. Article
  8. Targeting MYCN and ALK in resistant and relapsing neuroblastoma.Cancer drug resistance (Alhambra, Calif.) · 2019
    Review
  9. Article
  10. Review
  11. Article
  12. Review
  13. 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

6 authors at 2 institutions in 2 countries.

Jennifer R SmithDivision of Cancer Therapeutics, The Institute of Cancer Research, London, SM2 5NG, United Kingdom; Division of Clinical Studies, The Institute of Cancer Research, London, SM2 5NG, United Kingdom.
Lucas MorenoDivision of Clinical Studies, The Institute of Cancer Research, London, SM2 5NG, United Kingdom; Children's and Young People's Unit, Royal Marsden NHS Foundation Trust, Sutton, SM2 5PT, United Kingdom; CNIO, Spanish National Cancer Research Centre, Melchor Fernandez Almagro 3, 28029, Madrid, Spain.
Simon P HeatonDivision of Cancer Therapeutics, The Institute of Cancer Research, London, SM2 5NG, United Kingdom.
Louis CheslerDivision of Clinical Studies, The Institute of Cancer Research, London, SM2 5NG, United Kingdom; Children's and Young People's Unit, Royal Marsden NHS Foundation Trust, Sutton, SM2 5PT, United Kingdom.
Andrew D J PearsonDivision of Clinical Studies, The Institute of Cancer Research, London, SM2 5NG, United Kingdom; Children's and Young People's Unit, Royal Marsden NHS Foundation Trust, Sutton, SM2 5PT, United Kingdom.
Michelle D GarrettDivision of Cancer Therapeutics, The Institute of Cancer Research, London, SM2 5NG, United Kingdom; School of Biosciences, University of Kent, Canterbury, Kent, CT2 7NJ, United Kingdom. Electronic address: m.d.garrett@kent.ac.uk.
Institute of Cancer Research · GBRoyal Marsden NHS Foundation Trust · GB

Funding

Cancer Research UK 18339Cancer Research UK C309/A11566Cancer Research UK C347/A15403Department of Health
6 · The paper itself

Abstract

There is an urgent need for improved therapies for children with high-risk neuroblastoma where survival rates remain low. MYCN amplification is the most common genomic change associated with aggressive neuroblastoma and drugs targeting PI3K/AKT/mTOR, to activate MYCN oncoprotein degradation, are entering clinical evaluation. Our aim was to develop and validate pharmacodynamic (PD) biomarkers to evaluate both proof of mechanism and proof of concept for drugs that block PI3K/AKT/mTOR pathway activity in children with neuroblastoma. We have addressed the issue of limited access to tumor biopsies for quantitative detection of protein biomarkers by optimizing a three-color fluorescence activated cell sorting (FACS) method to purify CD45-/GD2+/CD56+ neuroblastoma cells from bone marrow. We then developed a novel quantitative measurement of MYCN protein in these isolated neuroblastoma cells, providing the potential to demonstrate proof of concept for drugs that inhibit PI3K/AKT/mTOR signaling in this disease. In addition we have established quantitative detection of three biomarkers for AKT pathway activity (phosphorylated and total AKT, GSK3β and P70S6K) in surrogate platelet-rich plasma (PRP) from pediatric patients. Together our new approach to neuroblastoma cell isolation for protein detection and suite of PD assays provides for the first time the opportunity for robust, quantitative measurement of protein-based PD biomarkers in this pediatric patient population. These will be ideal tools to support clinical evaluation of PI3K/AKT/mTOR pathway drugs and their ability to target MYCN oncoprotein in upcoming clinical trials in neuroblastoma.

Indexed as

Signal TransductionAdolescentAdultBiomarkers, TumorBone Marrow CellsChildChild, PreschoolFemaleHumansInfantMaleNeuroblastomaN-Myc Proto-Oncogene ProteinPharmacokineticsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktBiomarkers, TumorMTOR protein, humanMYCN protein, humanN-Myc Proto-Oncogene ProteinPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktTOR Serine-Threonine KinasesAKTBiomarkerMYCNNeuroblastomaPharmacodynamic

Identifiers

PMID26686971
PMCPMC5423144
OpenAlexW2172554008

What OpenQuestion holds

Textmetadata
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.