Evidence map›Paper›PMID 40140353›Full record

ArticleNature communications2025

Inhibition of human-HPV hybrid ecDNA enhancers reduces oncogene expression and tumor growth in oropharyngeal cancer.

Takuya Nakagawa, Jens Luebeck, Kaiyuan Zhu, Joshua T Lange, Roman Sasik, Chad Phillips, Sayed Sadat, Sara Javadzadeh, Qian Yang, Abdula Monther and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. 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
–field-weighted citation impact
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.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Takuya NakagawaMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA. tanakagawa@health.ucsd.edu.ORCID http://orcid.org/0000-0003-1216-4822
Jens LuebeckDepartment of Computer Science and Engineering, UC San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-4391-979X
Kaiyuan ZhuDepartment of Computer Science and Engineering, UC San Diego, La Jolla, CA, USA.
Joshua T LangeDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Roman SasikCenter for Computational Biology and Bioinformatics, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-9266-8993
Chad PhillipsMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Sayed SadatMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Sara JavadzadehDepartment of Computer Science and Engineering, UC San Diego, La Jolla, CA, USA.
Qian YangDepartment of Cellular and Molecular Medicine, Center for Epigenomics, University of California, San Diego, La Jolla, CA, USA.
Abdula MontherMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Santiago FassardiMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA.
Allen WangDepartment of Cellular and Molecular Medicine, Center for Epigenomics, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-9870-7888
Kersi PestonjamaspCancer Center Microscopy Core, University of California, San Diego, La Jolla, CA, USA.
Brin RosenthalCenter for Computational Biology and Bioinformatics, University of California, San Diego, La Jolla, CA, USA.
Kathleen M FischCenter for Computational Biology and Bioinformatics, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-0117-7444
Paul MischelDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-4560-2211
Vineet BafnaDepartment of Computer Science and Engineering, UC San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-5810-6241
Joseph A CalifanoMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA. jcalifano@health.ucsd.edu.ORCID http://orcid.org/0000-0002-4715-6761

Funding

UC San Diego Clinical and Translational Research InstituteUL1TR001442 · NCATS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FIRESTEIN, GARY S, HOGARTH, MICHAEL · 2015 to 2024
$88.3M
Software and algorithms for elucidating the structure, function, and evolution of extrachromosomal DNAU24CA264379 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI BAFNA, VINEET, MESIROV, JILL P. · 2021 to 2025
$3.5M
Computational methods for detecting patterns of complex genomic variationR01GM114362 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Vineet Bafna · 2016 to 2026
$3.1M
eDyNAmiC - UCSDOT2CA278635 · NCI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Vineet Bafna · 2022 to 2026
$1.8M
NCATS NIH HHS UL1 TR001442NCI NIH HHS OT2 CA278635NCI NIH HHS U24 CA264379NIGMS NIH HHS R01 GM114362
6 · The paper itself

Abstract

Extrachromosomal circular DNA (ecDNA) has been found in most types of human cancers, and ecDNA incorporating viral genomes has recently been described, specifically in human papillomavirus (HPV)-mediated oropharyngeal cancer (OPC). However, the molecular mechanisms of human-viral hybrid ecDNA (hybrid ecDNA) for carcinogenesis remains elusive. We characterize the epigenetic status of hybrid ecDNA using HPVOPC cell lines and patient-derived tumor xenografts, identifying HPV oncogenes E6/E7 in hybrid ecDNA are flanked by previously unrecognized somatic DNA enhancers and HPV L1 enhancers, with strong cis-interactions. Targeting of these enhancers by clustered regularly interspaced short palindromic repeats interference or hybrid ecDNA by bromodomain and extra-terminal inhibitor reduces E6/E7 expression, and significantly inhibites in vitro and/or in vivo growth only in ecDNA(+) models. HPV DNA in hybrid ecDNA structures are associated with previously unrecognized somatic and HPV enhancers in hybrid ecDNA that drive HPV ongogene expression and carcinogenesis, and can be targeted with ecDNA disrupting therapeutics.

Indexed as

ChromosomesDNAGene Expression Regulation, ViralHuman Papillomavirus VirusesOncogenesOropharyngeal NeoplasmsAgedAnimalsAzepinesCell LineCell ProliferationDisease ProgressionFemaleGenome, HumanGenome, ViralHumansAzepinesDNA(+)-JQ1 compoundTriazoles

Identifiers

PMID40140353
PMCPMC11947173

What OpenQuestion holds

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Registered trials

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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.