Evidence map›Paper›PMID 27048952›Full record

ArticleMolecular cancer therapeutics2016

Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic Biomarkers: Preclinical Discovery to Phase I Trial Evaluation.

Joo Ern Ang, Rupinder Pandher, Joo Chew Ang, Yasmin J Asad, Alan T Henley, Melanie Valenti, Gary Box, Alexis de Haven Brandon, Richard D Baird, Lori Friedman and 7 more

Registry-linked trialOpen access · greenAbstract readClinical Trial, Phase I
In one paragraph

Article in Molecular cancer therapeutics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06057077 (A Randomized Clinical Trial Comparing Semaglutide GLP1 Agonists With Degludec Basal-bolus Insulin in Early Type 1 Diabetes), which is not on this 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 29% 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.

NCT06057077 phase1 / phase2unknown statusstarted 2024, after this paper: background citation

A Randomized Clinical Trial Comparing Semaglutide GLP1 Agonists With Degludec Basal-bolus Insulin in Early Type 1 Diabetes

Ran2024Enrolled120Registered outcomes2Posted comparisons0ConditionsType 1 DiabetesArmsSemaglutide weekly injection
Open the trial in the graph
3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 18 citations in OpenAlex.

  1. Trial
  2. Thieno[3,2-International journal of molecular sciences · 2026
    Review
  3. Review
  4. Review
  5. Identification of Plasma Metabolites Associated with Lung Cancer Survival.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
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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

17 authors at 1 institution in 1 country.

Joo Ern AngCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, United Kingdom. Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom.
Rupinder PandherCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, United Kingdom.
Joo Chew AngSchool of Physics, University of Melbourne, Melbourne, Victoria, Australia.
Yasmin J AsadCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, United Kingdom.
Alan T HenleyCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, United Kingdom.
Melanie ValentiCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, United Kingdom.
Gary BoxCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, United Kingdom.
Alexis de Haven BrandonCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, United Kingdom.
Richard D BairdCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, United Kingdom. Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom.
Lori FriedmanGenentech Inc., South San Francisco, California.
Mika DerynckGenentech Inc., South San Francisco, California.
Bart VanhaesebroeckUCL Cancer Institute, University College London, London, United Kingdom.
Suzanne A EcclesCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, United Kingdom.
Stan B KayeCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, United Kingdom. Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom.
Paul WorkmanCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, United Kingdom.
Johann S de BonoCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, United Kingdom. Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom.
Florence I RaynaudCancer Research UK Cancer Therapeutics Unit, The Institute of Cancer Research, London, United Kingdom. Drug Development Unit, The Royal Marsden NHS Foundation Trust, Sutton, United Kingdom. Florence.Raynaud@icr.ac.uk.
CRUK Lung Cancer Centre of Excellence · GB

Funding

Cancer Research UK 11566Cancer Research UK 15965Cancer Research UK A11566Cancer Research UK A11566_1Cancer Research UK A11566_2Cancer Research UK C2338/A15965Cancer Research UK C309/A8992Medical Research Council G0502133Wellcome TrustWellcome Trust 090952/Z/09/Z
6 · The paper itself

Abstract

PI3K plays a key role in cellular metabolism and cancer. Using a mass spectrometry-based metabolomics platform, we discovered that plasma concentrations of 26 metabolites, including amino acids, acylcarnitines, and phosphatidylcholines, were decreased in mice bearing PTEN-deficient tumors compared with non-tumor-bearing controls and in addition were increased following dosing with class I PI3K inhibitor pictilisib (GDC-0941). These candidate metabolomics biomarkers were evaluated in a phase I dose-escalation clinical trial of pictilisib. Time- and dose-dependent effects were observed in patients for 22 plasma metabolites. The changes exceeded baseline variability, resolved after drug washout, and were recapitulated on continuous dosing. Our study provides a link between modulation of the PI3K pathway and changes in the plasma metabolome and demonstrates that plasma metabolomics is a feasible and promising strategy for biomarker evaluation. Also, our findings provide additional support for an association between insulin resistance, branched-chain amino acids, and related metabolites following PI3K inhibition. Mol Cancer Ther; 15(6); 1412-24. ©2016 AACR.

Indexed as

AnimalsBiomarkers, TumorCell Line, TumorDose-Response Relationship, DrugHumansIndazolesMass SpectrometryMetabolomeMetabolomicsMiceNeoplasmsNeoplasm TransplantationPTEN PhosphohydrolaseSulfonamidesTime Factors2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidineBiomarkers, TumorIndazolesPTEN PhosphohydrolaseSulfonamides

Identifiers

PMID27048952
PMCPMC5321508
OpenAlexW2326237524

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

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.