Evidence map›Paper›PMID 33742144›Full record

ArticleBritish journal of cancer2021

Development of a rational strategy for integration of lactate dehydrogenase A suppression into therapeutic algorithms for head and neck cancer.

Yunyun Chen, Anastasios Maniakas, Lin Tan, Meng Cui, Xiangdong Le, Joshua S Niedzielski, Keith A Michel, Collin J Harlan, Wuhao Lu, Ying C Henderson and 6 more

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

Article in British journal of cancer, 2021. 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
0.9field-weighted citation impact, top 32% 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, 14 citations in OpenAlex.

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  10. First-in-Human Hyperpolarized MRI for Tumor Metabolism in HNSCC.JAMA otolaryngology-- head & neck surgery · 2024
    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

16 authors at 2 institutions in 3 countries.

Yunyun ChenDepartment of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Anastasios ManiakasDepartment of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Lin TanDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Meng CuiDepartment of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Xiangdong LeDepartment of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Joshua S NiedzielskiDepartment of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Keith A MichelDepartment of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Collin J HarlanDepartment of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Wuhao LuDepartment of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA.
Ying C HendersonDepartment of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Abdallah S R MohamedDepartment of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Philip L LorenziDepartment of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Nagireddy PutluriDepartment of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA.
James A BanksonDepartment of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Vlad C SandulacheDepartment of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, TX, USA. Vlad.Sandulache@bcm.edu.ORCID http://orcid.org/0000-0002-9205-385X
Stephen Y LaiDepartment of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. sylai@mdanderson.org.ORCID http://orcid.org/0000-0001-8301-7286
The University of Texas MD Anderson Cancer Center · USBaylor College of Medicine · US

Funding

Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8M
Tumor BiologyP30CA125123 · NCI · BAYLOR COLLEGE OF MEDICINE · PI Michael M Ittmann · 2007 to 2026
$73.9M
Multi-Site Development & Evaluation of a Quantitative 3D Hyperpolarized C-13 MRI Clinical Prostate Cancer ExamR01CA211150 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI BANKSON, JAMES A · 2017 to 2021
$3.2M
Computational Tools for Analysis and Visualization of Quality Control Issues in Metabolomic DataU01CA235510 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI AKBANI, REHAN, BROOM, BRADLEY MCINTOSH · 2018 to 2021
$1.6M
Orbitrap Elite High-Resolution Mass Spectrometer for Proteomics and MetabolomicsS10OD012304 · OD · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI HAWKE, DAVID H · 2013 to 2013
$877k
Overcoming cisplatin resistance by targeting fatty acid metabolismR03DE028858 · NIDCR · BAYLOR COLLEGE OF MEDICINE · PI SANDULACHE, VLAD C · 2019 to 2020
$334k
NCI NIH HHS P30 CA125123NCI NIH HHS R01 CA211150NIDCR NIH HHS R03 DE028858
6 · The paper itself

Abstract

backgroundLactate dehydrogenase (LDH) is a critical metabolic enzyme. LDH A (LDHA) overexpression is a hallmark of aggressive malignancies and has been linked to tumour initiation, reprogramming and progression in multiple tumour types. However, successful LDHA inhibition strategies have not materialised in the translational and clinical space. We sought to develop a rational strategy for LDHA suppression in the context of solid tumour treatment.

methodsWe utilised a doxycycline-inducible short hairpin RNA (shRNA) system to generate LDHA suppression. Lactate and LDH activity levels were measured biochemically and kinetically using hyperpolarised

resultsshRNA suppression of LDHA generated a time-dependent decrease in LDH activity with transient shifts in intracellular lactate levels, a decrease in carbon flux from pyruvate into lactate and compensatory shifts in metabolic flux in glycolysis and the Krebs cycle. LDHA suppression decreased cellular proliferation and temporarily stunted tumour growth in ATC and HNSCC xenografts but did not by itself result in tumour cure, owing to the maintenance of residual viable cells. Only when chronic LDHA suppression was combined with radiation was a functional cure achieved.

conclusionsSuccessful targeting of LDHA requires exquisite dose and temporal control without significant concomitant off-target toxicity. Combinatorial strategies with conventional radiation are feasible as long as the suppression is targeted, prolonged and non-toxic.

Indexed as

AlgorithmsAnimalsAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorDown-RegulationEnzyme InhibitorsFeasibility StudiesFemaleGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticGene Knockdown TechniquesHead and Neck NeoplasmsHumansL-Lactate DehydrogenaseMetabolomicsMiceEnzyme InhibitorsLDHA protein, humanL-Lactate DehydrogenaseRNA, Small Interfering

Identifiers

PMID33742144
PMCPMC8110762
OpenAlexW3139510287

What OpenQuestion holds

Textmetadata
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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.