Evidence map›Paper›PMID 36164710›Full record

ArticleBritish journal of clinical pharmacology2023

Tumour, whole-blood, plasma and tissue concentrations of metformin in lung cancer patients.

Joseph D Phillips, Darcy B Pooler, Dylan B Ness, Kayla Fay, Steven Tau, Eugene Demidenko, Riley A Hampsch, Lionel D Lewis, Todd W Miller

Open access · greenAbstract read
In one paragraph

Article in British journal of clinical pharmacology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
0.8field-weighted citation impact, top 31% 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

8 citing papers in PubMed, 9 citations in OpenAlex.

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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

9 authors at 2 institutions in 1 country.

Joseph D PhillipsDepartment of Surgery, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Lebanon, New Hampshire, USA.
Darcy B PoolerDepartment of Medicine, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Lebanon, New Hampshire, USA.ORCID 0000-0001-9762-9013
Dylan B NessDartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
Kayla FayDartmouth-Hitchcock Medical Center, Lebanon, New Hampshire, USA.
Steven TauDepartment of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Lebanon, New Hampshire, USA.
Eugene DemidenkoDepartment of Biomedical Data Science, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Lebanon, New Hampshire, USA.
Riley A HampschDepartment of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Lebanon, New Hampshire, USA.
Lionel D LewisDepartment of Medicine, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Lebanon, New Hampshire, USA.ORCID 0000-0003-1164-5157
Todd W MillerDepartment of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Norris Cotton Cancer Center, Lebanon, New Hampshire, USA.ORCID 0000-0001-8912-2909
Dartmouth College · USDartmouth–Hitchcock Medical Center · US

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Fred W Kolling IV · 1985 to 2026
$91.3M
SYNERGY: The Dartmouth Center for clinical and Translational ScienceUL1TR001086 · NCATS · DARTMOUTH COLLEGE · PI GREEN, ALAN I · 2013 to 2017
$18.3M
Timing is everything: applications in precision oncology for ER+ breast cancerR01CA211869 · NCI · DARTMOUTH COLLEGE · PI MILLER, TODD W. · 2017 to 2021
$2.1M
NCATS NIH HHS UL1 TR001086NCI NIH HHS P30 CA023108NCI NIH HHS R01 CA211869
6 · The paper itself

Abstract

aimMetformin is used for the management of type 2 diabetes mellitus (T2DM) and is being tested clinically as an anticancer agent. Metformin concentrations safely achievable in human solid tissues including tumours are unknown. This study was designed to determine metformin concentration in tissue compartments as a function of dose to inform rational dosing in preclinical models and interpretation of clinical results."

methodsSubjects with solid tumours to be treated by resection and either (A) willingness to take metformin for 7-10 days before surgery or (B) taking metformin for T2DM were eligible. Whole blood, plasma, tumour, tumour-adjacent uninvolved tissue and subcutaneous adipose tissue were obtained for liquid chromatography with tandem mass spectrometry to measure metformin concentrations.

resultsAll subjects had primary lung tumours. Metformin dose was significantly correlated with drug concentrations in all tissues analysed. Intersubject metformin concentrations varied by over two orders of magnitude. Metformin concentrations were significantly higher in tumour tissues and lower in adipose tissues compared to other tissues. Concentrations in blood and plasma were significantly correlated with concentrations in solid tissues.

conclusionMetformin accumulates in cellular compartments. Concentrations observed in plasma, blood, lung and tumour tissues in subjects treated with US Food and Drug Administration-approved doses for T2DM are lower than those typically used in tissue culture studies. However, such tissue concentrations are in line with those found within cultured cells treated with supra-pharmacological doses of metformin. Given the large intersubject variability in metformin concentrations, it is imperative to determine whether there is an association between tissue metformin concentration and anticancer activity in humans.

Indexed as

Diabetes Mellitus, Type 2Lung NeoplasmsMetforminAdipose TissueHumansHypoglycemic AgentsPlasmaHypoglycemic AgentsMetformincancermetformintissue distribution

Identifiers

PMID36164710
PMCPMC9931625
OpenAlexW4297254360

What OpenQuestion holds

Texttitle and abstract
LicenceTDM
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.