Evidence map›Paper›PMID 34261799›Full record

ArticleScience translational medicine2021

Losartan prevents tumor-induced hearing loss and augments radiation efficacy in NF2 schwannoma rodent models.

Limeng Wu, Sasa Vasilijic, Yao Sun, Jie Chen, Lukas D Landegger, Yanling Zhang, Wenjianlong Zhou, Jun Ren, Samuel Early, Zhenzhen Yin and 14 more

Open access · greenAbstract read
In one paragraph

Article in Science translational medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
3.2field-weighted citation impact, top 7% 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

35 citing papers in PubMed, 49 citations in OpenAlex.

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  13. Current Status of Research on Losartan in Tumour Therapy.Journal of cellular and molecular medicine · 2026
    Review
  14. Article
  15. Review
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  18. Plasma Matrix Metalloproteinase-9 Predicts Intraoperative Experience and Extent of Resection in Vestibular Schwannoma Surgery.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2025
    Article
  19. Article
  20. Review
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

24 authors at 5 institutions in 2 countries.

Limeng WuEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0002-9382-6447
Sasa VasilijicEaton-Peabody Laboratories and Department of Otolaryngology, Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0002-3923-3448
Yao SunEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0003-4423-4178
Jie ChenEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0002-3591-1379
Lukas D LandeggerEaton-Peabody Laboratories and Department of Otolaryngology, Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0002-9660-2625
Yanling ZhangEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Wenjianlong ZhouEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Jun RenEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0002-6358-0765
Samuel EarlyEaton-Peabody Laboratories and Department of Otolaryngology, Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston, MA 02114, USA.
Zhenzhen YinEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0002-6022-5661
William W HoEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0002-1272-8184
Na ZhangEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0001-6978-2731
Xing GaoEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0002-2700-420X
Grace Y LeeSt. Mark's School, Southborough, MA 01772, USA.ORCID 0000-0001-6210-9173
Meenal DattaEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0001-5727-8992
Jessica E SagersEaton-Peabody Laboratories and Department of Otolaryngology, Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0002-1176-524X
Alyssa BrownEaton-Peabody Laboratories and Department of Otolaryngology, Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0002-1064-8818
Alona MuzikanskyDivision of Biostatistics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Anat Stemmer-RachamimovMolecular Pathology Division, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0003-3846-5295
Luo ZhangDepartment of Otolaryngology, Head and Neck Surgery, Beijing TongRen Hospital, Capital Medical University, Beijing 100730, China.ORCID 0000-0002-0910-9884
Scott R PlotkinDepartment of Neurology and Cancer Center, Massachusetts General Hospital, Boston, MA 02114, USA.ORCID 0000-0002-6109-6419
Rakesh K JainEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.ORCID 0000-0001-7571-3548
Konstantina M StankovicEaton-Peabody Laboratories and Department of Otolaryngology, Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston, MA 02114, USA. lei@steele.mgh.harvard.edu kstankovic@stanford.edu.ORCID 0000-0003-0233-279X
Lei XuEdwin L. Steele Laboratories, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA. lei@steele.mgh.harvard.edu kstankovic@stanford.edu.ORCID 0000-0003-0525-183X
Harvard University · USMassachusetts Eye and Ear Infirmary · USMassachusetts General Hospital · USBeijing Tongren Hospital · CNSt. Mark's Hospital · US

Funding

Vascular Normalization: Rolse of Perivascular CellsP01CA080124 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI SEED, BRIAN · 2000 to 2016
$35.0M
Targeting the Vasular SystemP50CA165962 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI Tracy T Batchelor · 2013 to 2026
$33.5M
AZD2171 and chemoradiation for newly diagnosed glioblastomaR01CA129371 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BATCHELOR, TRACY T · 2007 to 2017
$6.2M
Dissecting Pediatric Brain Tumor Microenvironment to Improve TreatmentR35CA197743 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K. · 2015 to 2020
$5.7M
Targeting physical stress-driven mechanisms to overcome glioblastoma treatment resistanceU01CA261842 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI JAIN, RAKESH K., MUNN, LANCE L. · 2021 to 2025
$3.1M
Reprogramming PDAC tumor microenvironment to improve immunotherapyU01CA224348 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI BOUCHER, YVES, JAIN, RAKESH K. · 2017 to 2021
$2.9M
Reengineering obesity-induced abnormal microenvironment to improve PDAC treatmentR01CA208205 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI FUKUMURA, DAI, JAIN, RAKESH K. · 2017 to 2020
$2.2M
Mechanisms of sensorineural hearing loss: secreted factorsR01DC015824 · NIDCD · STANFORD UNIVERSITY · PI STANKOVIC, KONSTANTINA M · 2016 to 2020
$2.2M
NCI NIH HHS P01 CA080124NCI NIH HHS P50 CA165962NCI NIH HHS R01 CA129371NCI NIH HHS R01 CA208205NCI NIH HHS R35 CA197743NCI NIH HHS U01 CA224348NCI NIH HHS U01 CA261842NIDCD NIH HHS R01 DC015824
6 · The paper itself

Abstract

Hearing loss is one of the most common symptoms of neurofibromatosis type 2 (NF2) caused by vestibular schwannomas (VSs). Fibrosis in the VS tumor microenvironment (TME) is associated with hearing loss in patients with NF2. We hypothesized that reducing the fibrosis using losartan, an FDA-approved antihypertensive drug that blocks fibrotic and inflammatory signaling, could improve hearing. Using NF2 mouse models, we found that losartan treatment normalized the TME by (i) reducing neuroinflammatory IL-6/STAT3 signaling and preventing hearing loss, (ii) normalizing tumor vasculature and alleviating neuro-edema, and (iii) increasing oxygen delivery and enhancing efficacy of radiation therapy. In preparation to translate these exciting findings into the clinic, we used patient samples and data and demonstrated that IL-6/STAT3 signaling inversely associated with hearing function, that elevated production of tumor-derived IL-6 was associated with reduced viability of cochlear sensory cells and neurons in ex vivo organotypic cochlear cultures, and that patients receiving angiotensin receptor blockers have no progression in VS-induced hearing loss compared with patients on other or no antihypertensives based on a retrospective analysis of patients with VS and hypertension. Our study provides the rationale and critical data for a prospective clinical trial of losartan in patients with VS.

Indexed as

Hearing LossNeurilemmomaNeurofibromatosis 2AnimalsHumansLosartanMiceProspective StudiesRetrospective StudiesRodentiaTreatment OutcomeTumor MicroenvironmentLosartan

Identifiers

PMID34261799
PMCPMC8409338
OpenAlexW3179963300

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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.