ArticleEMBO molecular medicine2017
Reversible p53 inhibition prevents cisplatin ototoxicity without blocking chemotherapeutic efficacy.
Article in EMBO molecular medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
58 citing papers in PubMed, 1 synthesis or guideline pooled it, 105 citations in OpenAlex.
- The genetic vulnerability to cisplatin ototoxicity: a systematic review.Scientific reports · 2019Pooled it
- Herbal Formula AC591 Protects Against Cisplatin-Induced Hearing Loss by Inhibiting p53-Mediated Ferroptosis.Smart medicine · 2026Article
- Current clinical applications and future developments of platinum-based anticancer drugs.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026Review
- Human induced pluripotent stem cell-derived inner ear organoids reveal hair cell damage and plasticity after cisplatin and gentamicin exposure.Disease models & mechanisms · 2026Article
- From Ototoxicity to Otoprotection: Mechanism and Protective Strategies in Cisplatin Therapy.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Cisplatin-Induced APE2 Overexpression Disrupts MYH9 Function and Causes Hearing Loss.Cancer research communications · 2025Article
- Fasudil protects spiral ganglion neurons and hair cells against cisplatin-induced apoptosis by inhibiting reactive oxygen species accumulation and regulating the ROCK/PTEN/AKT signaling pathway.Toxicology research · 2025Article
- Strategies to Mitigate Cisplatin-Induced Ototoxicity: A Literature Review of Protective Agents, Mechanisms, and Clinical Gaps.Audiology research · 2025Review
- Mechanistic insights into cisplatin-induced ototoxicity: the central role of transient receptor potential channels.Frontiers in molecular biosciences · 2025Review
- Studies on the mechanism of ototoxic action of cisplatin and the antagonistic effect of polyphenolic compounds.Frontiers in pharmacology · 2025Review
- Enhancing biocompatibility of the brain-machine interface: A review.Bioactive materials · 2024Review
- An In Vitro Oxidative Stress Model of the Human Inner Ear Using Human-Induced Pluripotent Stem Cell-Derived Otic Progenitor Cells.Antioxidants (Basel, Switzerland) · 2024Article
- Pharmacological Approaches to Hearing Loss.Pharmacological reviews · 2024Review
- BRCA1 Promotes Repair of DNA Damage in Cochlear Hair Cells and Prevents Hearing Loss.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Nuciferine Protects Cochlear Hair Cells from Ferroptosis through Inhibiting NCOA4-Mediated Ferritinophagy.Antioxidants (Basel, Switzerland) · 2024Article
- The human OPA1Cellular and molecular life sciences : CMLS · 2024Article
- NADPH Oxidase 3: Beyond the Inner Ear.Antioxidants (Basel, Switzerland) · 2024Review
- Oxidative Stress Plays an Important Role in Glutamatergic Excitotoxicity-Induced Cochlear Synaptopathy: Implication for Therapeutic Molecules Screening.Antioxidants (Basel, Switzerland) · 2024Article
- Oxidative stress and inflammation cause auditory system damage via glial cell activation and dysregulated expression of gap junction proteins in an experimental model of styrene-induced oto/neurotoxicity.Journal of neuroinflammation · 2024Article
- Hearing loss during chemotherapy: prevalence, mechanisms, and protection.American journal of cancer research · 2024Review
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cisplatin is a widely used chemotherapy drug, despite its significant ototoxic side effects. To date, the mechanism of cisplatin-induced ototoxicity remains unclear, and hearing preservation during cisplatin-based chemotherapy in patients is lacking. We found activation of the ATM-Chk2-p53 pathway to be a major determinant of cisplatin ototoxicity. However, prevention of cisplatin-induced ototoxicity is hampered by opposite effects of ATM activation upon sensory hair cells: promoting both outer hair cell death and inner hair cell survival. Encouragingly, however, genetic or pharmacological ablation of p53 substantially attenuated cochlear cell apoptosis, thus preserving hearing. Importantly, systemic administration of a p53 inhibitor in mice bearing patient-derived triple-negative breast cancer protected auditory function, without compromising the anti-tumor efficacy of cisplatin. Altogether, these findings highlight a novel and effective strategy for hearing protection in cisplatin-based chemotherapy.
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Registered trials
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.