Evidence map›Paper›PMID 35053444›Full record

ArticleCancers2022

Repositioning Fenofibrate to Reactivate p53 and Reprogram the Tumor-Immune Microenvironment in HPV+ Head and Neck Squamous Cell Carcinoma.

W Quinn O'Neill, Xiujie Xie, Shanying Gui, Heping Yu, Jacqueline Davenport, Thomas Cartwright, Marta Storl-Desmond, Esther Ryu, Ernest R Chan, Shufen Cao and 3 more

Open access · goldAbstract read
In one paragraph

Article in Cancers, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
1.4field-weighted citation impact, top 18% 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

9 citing papers in PubMed, 13 citations in OpenAlex.

  1. Review
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  3. PPARα Agonism Enhances Immune Response to Radiotherapy While Dietary Oleic Acid Results in Counteraction.Clinical cancer research : an official journal of the American Association for Cancer Research · 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

13 authors at 4 institutions in 1 country.

W Quinn O'NeillUniversity Hospitals Seidman Cancer Center, Cleveland, OH 44106, USA.
Xiujie XieDepartment of Otolaryngology-Head and Neck Surgery, The Ohio State University Wexner Medical Center, Columbus, OH 43210, USA.
Shanying GuiUniversity Hospitals Seidman Cancer Center, Cleveland, OH 44106, USA.
Heping YuDepartment of Otolaryngology-Head and Neck Surgery, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Jacqueline DavenportDepartment of Otolaryngology-Head and Neck Surgery, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Thomas CartwrightDepartment of Otolaryngology-Head and Neck Surgery, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.ORCID 0000-0002-7980-4233
Marta Storl-DesmondDepartment of Otolaryngology-Head and Neck Surgery, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Esther RyuDepartment of Otolaryngology-Head and Neck Surgery, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.ORCID 0000-0002-8897-6117
Ernest R ChanCase Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Shufen CaoCase Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Pingfu FuCase Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Theodoros N TeknosUniversity Hospitals Seidman Cancer Center, Cleveland, OH 44106, USA.
Quintin PanUniversity Hospitals Seidman Cancer Center, Cleveland, OH 44106, USA.
University School · USUniversity Hospitals Seidman Cancer Center · USCase Western Reserve University · USThe Ohio State University Wexner Medical Center · US

Funding

Role of P300 in HPV-positive Head and Neck CancerR01DE023555 · NIDCR · OHIO STATE UNIVERSITY · PI ARORA, PARAMJIT S, PAN, QUINTIN · 2015 to 2019
$2.5M
Cancer Initiating Cells and Treatment ResistanceR01CA193590 · NCI · OHIO STATE UNIVERSITY · PI PAN, QUINTIN · 2015 to 2020
$1.8M
NCI NIH HHS R01CA193590NIDCR NIH HHS R01 DE023555NIDCR NIH HHS R01DE023555University Hospitals Seidman Cancer Center N/A
6 · The paper itself

Abstract

Human papillomavirus-associated head and neck squamous cell carcinoma (HPV+ HNSCC) is recognized as a distinct disease with unique etiology and clinical features. Current standard of care therapeutic modalities are identical for HPV+ and HPV- HNSCC and thus, there remains an opportunity to develop innovative pharmacologic approaches to exploit the inherent vulnerabilities of HPV+ HNSCC. In this study, using an inducible HPVE6E7 knockdown system, we found that HPV+ HNSCC cells are addicted to HPVE6E7, such that loss of these viral oncogenes impaired tumorigenicity in vitro and in vivo. A number of druggable pathways, including PPAR and Wnt, were modulated in response to HPVE6E7 loss. Fenofibrate showed significant anti-proliferative effects in a panel of HPV+ cancer cell lines. Additionally, fenofibrate impaired tumor growth as monotherapy and potentiated the activity of cisplatin in a pre-clinical HPV+ animal model. Systemic fenofibrate treatment induced p53 protein accumulation, and surprisingly, re-programmed the tumor-immune microenvironment to drive immune cell infiltration. Since fenofibrate is FDA-approved with a favorable long-term safety record, repositioning of this drug, as a single agent or in combination with cisplatin or checkpoint blockade, for the HPV+ HNSCC setting should be prioritized.

Indexed as

anti-cancer therapyhuman papillomavirushypoxiaPD-1PD-L1tumor microenvironment

Identifiers

PMID35053444
PMCPMC8773501
OpenAlexW4205533786

What OpenQuestion holds

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LicenceCC BY
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.