Evidence map›Paper›PMID 36284040›Full record

ArticleMolecular imaging and biology2023

Early Reduction of Glucose Consumption Is a Biomarker of Kinase Inhibitor Efficacy Which Can Be Reversed with GLUT1 Overexpression in Lung Cancer Cells.

Chiara Ghezzi, Stefani Perez, Kaitlin Ryan, Alicia Wong, Bao Ying Chen, Robert Damoiseaux, Peter M Clark

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

Article in Molecular imaging and biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
1.2field-weighted citation impact, top 20% 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

4 citing papers in PubMed, 8 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

7 authors at 2 institutions in 1 country.

Chiara GhezziCrump Institute for Molecular Imaging, University of California, Los Angeles, Box 951770, Los Angeles, CA, 90095-1770, USA.
Stefani Perez *Crump Institute for Molecular Imaging, University of California, Los Angeles, Box 951770, Los Angeles, CA, 90095-1770, USA.
Kaitlin Ryan *Crump Institute for Molecular Imaging, University of California, Los Angeles, Box 951770, Los Angeles, CA, 90095-1770, USA.
Alicia WongCrump Institute for Molecular Imaging, University of California, Los Angeles, Box 951770, Los Angeles, CA, 90095-1770, USA.
Bao Ying ChenCrump Institute for Molecular Imaging, University of California, Los Angeles, Box 951770, Los Angeles, CA, 90095-1770, USA.
Robert DamoiseauxCrump Institute for Molecular Imaging, University of California, Los Angeles, Box 951770, Los Angeles, CA, 90095-1770, USA.
Peter M ClarkCrump Institute for Molecular Imaging, University of California, Los Angeles, Box 951770, Los Angeles, CA, 90095-1770, USA. pclark@mednet.ucla.edu.ORCID http://orcid.org/0000-0002-0786-9054
University of California, Los Angeles · USCalifornia NanoSystems Institute · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1 TR001881NCI NIH HHS P30 CA016042
6 · The paper itself

Abstract

purposeSmall molecule inhibitors that target oncogenic driver kinases are an important class of therapies for non-small cell lung cancer (NSCLC) and other malignancies. However, these therapies are not without their challenges. Each inhibitor works on only a subset of patients, the pharmacokinetics of these inhibitors is variable, and these inhibitors are associated with significant side effects. Many of these inhibitors lack non-invasive biomarkers to confirm pharmacodynamic efficacy, and our understanding of how these inhibitors block cancer cell growth remains incomplete. Limited clinical studies suggest that early (< 2 weeks after start of therapy) changes in tumor glucose consumption, measured by [

methodsWe tested nine NSCLC cell lines (A549, H1129, H1734, H1993, H2228, H3122, H460, HCC827, and PC9 cells) and ten targeted therapies (afatinib, buparlisib, ceritinib, cabozantinib, crizotinib, dovitinib, erlotinib, ponatinib, trametinib, and vemurafenib) across concentrations ranging from 1.6 nM to 5 µM to evaluate whether these inhibitors block glucose consumption at 24-h post-drug treatment and cell growth at 72-h post-drug treatment. We overexpressed the facilitative glucose transporter SLC2A1 (GLUT1) to test the functional connection between blocked glucose consumption and cell growth after treatment with a kinase inhibitor. A subset of these inhibitors and cell lines were studied in vivo.

resultsAcross the nine NSCLC cell lines, ten targeted therapies, and a range of inhibitor concentrations, whether a kinase inhibitor blocked glucose consumption at 24-h post-drug treatment strongly correlated with whether that inhibitor blocked cell growth at 72-h post-drug treatment in cell culture. These results were confirmed in vivo with [

conclusionsOur results demonstrate that the early inhibition of lung cancer glucose consumption in response to a kinase inhibitor is a strong biomarker of and is often required for the subsequent inhibition of cell growth. Early inhibition of glucose consumption may provide complementary information to other biomarkers in determining whether a drug will effectively limit tumor growth.

Indexed as

Antineoplastic AgentsCarcinoma, Non-Small-Cell LungLung NeoplasmsBiomarkersCell Line, TumorFluorodeoxyglucose F18GlucoseGlucose Transporter Type 1HumansPositron-Emission TomographyProtein Kinase InhibitorsAntineoplastic AgentsBiomarkersFluorodeoxyglucose F18GlucoseGlucose Transporter Type 1Protein Kinase Inhibitors[18F]FDGBiomarkerGlucose consumptionHigh-throughput screenLung cancerPositron emission tomographyTumor imaging

Identifiers

PMID36284040
PMCPMC10732700
OpenAlexW4307210682

What OpenQuestion holds

Textmetadata
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.