Evidence map›Paper›PMID 37934596›Full record

ArticleJCI insight2023

Dabrafenib protects from cisplatin-induced hearing loss in a clinically relevant mouse model.

Matthew A Ingersoll, Richard D Lutze, Chithra K Pushpan, Regina G Kelmann, Huizhan Liu, Mark T May, William J Hunter, David Zz He, Tal Teitz

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2023. 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
3.4field-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

13 citing papers in PubMed, 13 citations in OpenAlex.

  1. Trial
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  11. KSR1 Knockout Mouse Model Demonstrates MAPK Pathway's Key Role in Cisplatin- and Noise-induced Hearing Loss.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024
    Article
  12. Review
  13. Article
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

9 authors at 1 institution in 1 country.

Matthew A IngersollDepartment of Pharmacology and Neuroscience.
Richard D LutzeDepartment of Pharmacology and Neuroscience.
Chithra K PushpanDepartment of Pharmacology and Neuroscience.
Regina G KelmannDepartment of Pharmacology and Neuroscience.
Huizhan LiuDepartment of Biomedical Sciences, and.
Mark T MayDepartment of Pharmacology and Neuroscience.
William J HunterDepartment of Pathology, School of Medicine, Creighton University, Omaha, Nebraska, USA.
David Zz HeDepartment of Biomedical Sciences, and.
Tal TeitzDepartment of Pharmacology and Neuroscience.
Creighton University · US

Funding

UNMC Structural Biology CoreP20GM103427 · NIGMS · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI PAUL L SORGEN · 2012 to 2026
$59.2M
ZINC FINGER-INSPIRED FLUORESCENT CHEMOSENSORSP20RR016469 · NCRR · UNIVERSITY OF NEBRASKA MEDICAL CENTER · PI TURPEN, JAMES B · 2001 to 2011
$36.2M
Understanding the progression of hearing loss in an endolymphatic hydrops modelP20GM139762 · NIGMS · CREIGHTON UNIVERSITY · PI Hui Hong · 2021 to 2026
$16.1M
Repurposing an FDA approved Drug, B-Raf Kinase Inhibitor Dabrafenib for Protection from Cisplatin- and Noise- induced Hearing LossR01DC018850 · NIDCD · SCINTILLON INSTITUTE FOR PHOTOBIOLOGY · PI TEITZ, TAL · 2021 to 2025
$2.3M
Replacing an Animal Resource Facility Cage Washer.G20RR024001 · NCRR · CREIGHTON UNIVERSITY · PI DRESCHER, KRISTEN · 2007 to 2007
$638k
Repurposing FDA-Approved MEK Inhibitor Trametinib for Protection Against Cisplatin-Induced Hearing LossF32DC020102 · NIDCD · CREIGHTON UNIVERSITY · PI INGERSOLL, MATTHEW A · 2021 to 2023
$121k
NCRR NIH HHS G20 RR024001NCRR NIH HHS P20 RR016469NIDCD NIH HHS F32 DC020102NIDCD NIH HHS R01 DC018850NIGMS NIH HHS P20 GM103427NIGMS NIH HHS P20 GM139762
6 · The paper itself

Abstract

The widely used chemotherapy cisplatin causes permanent hearing loss in 40%-60% of patients with cancer. One drug, sodium thiosulfate, is approved by the FDA for use in pediatric patients with localized solid tumors for preventing cisplatin-induced hearing loss, but more drugs are desperately needed. Here, we tested dabrafenib, an FDA-approved BRAF kinase inhibitor and anticancer drug, in a clinically relevant multidose cisplatin mouse model. The protective effects of dabrafenib, given orally twice daily with cisplatin, were determined by functional hearing tests and cochlear outer hair cell counts. Toxicity of the drug cotreatment was evaluated, and levels of phosphorylated ERK were measured. A dabrafenib dose of 3 mg/kg BW, twice daily, in mice, was determined to be the minimum effective dose, and it is equivalent to one-tenth of the daily FDA-approved dose for human cancer treatment. The levels of hearing protection acquired, 20-25 dB at the 3 frequencies tested, in both female and male mice, persisted for 4 months after completion of treatments. Moreover, dabrafenib exhibited a good in vivo therapeutic index (> 25), protected hearing in 2 mouse strains, and diminished cisplatin-induced weight loss. This study demonstrates that dabrafenib is a promising candidate drug for protection from cisplatin-induced hearing loss.

Indexed as

Antineoplastic AgentsDeafnessHearing LossNeoplasmsAnimalsChildCisplatinFemaleHumansImidazolesMaleMiceOximesAntineoplastic AgentsCisplatindabrafenibImidazolesOximesCancerDrug therapyOtologyProtein kinasesTherapeutics

Identifiers

PMID37934596
PMCPMC10807719
OpenAlexW4388446534

What OpenQuestion holds

Textmetadata
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.