Gadd45a knockout alleviates cisplatin-induced hearing loss by inhibiting CXCL family protein expression

Cisplatin is a widely used chemotherapeutic agent, but its clinical application is limited by serious ototoxic side effects, including hearing loss, tinnitus, and vertigo. Inflammation is now recognized as a significant contributor to cisplatin-induced hearing loss, but the upstream regulators remain largely undefined....

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✦ The floor

Discussion

Signed responses from readers of the wire.

✦ Clinical Takeaway ✦

This is a mouse study identifying a potential molecular target for preventing cisplatin-related hearing damage; no actionable change in clinical practice is warranted at this stage.

✦ Why It Matters ✦

Identifying Gadd45a as a driver of cisplatin ototoxicity opens a new molecular pathway that could eventually lead to protective therapies for cancer patients at risk of treatment-related hearing loss.

✦ Key Points ✦

01Gadd45a knockout mice showed reduced cisplatin-induced hearing loss compared to wild-type controls.
02Protection was associated with suppressed expression of CXCL family chemokines and downstream inflammatory signalling.
03Study is preclinical (mouse model only); human translation is not yet established.
04Published in Military Medical Research (2026), a peer-reviewed journal.

✦ Claims & Evidence ✦

ClaimEvidenceSupport

Knockout of Gadd45a alleviates cisplatin-induced hearing loss in mice.

studysupported

Gadd45a knockout suppresses CXCL family protein expression in the context of cisplatin treatment.

studysupported

Inhibiting CXCL-associated inflammatory pathways is the mechanism by which Gadd45a knockout confers otoprotection.

studypartially supported

✦ Research metadata ✦

PMID: 42633148
DOI: 10.1016/j.mmr.2026.100063.
Journal: Military Medical Research
Publication type: research_article
Evidence level: 4
Population: Mouse model of cisplatin-induced hearing loss (Gadd45a knockout vs. wild-type mice)
Intervention: Gadd45a gene knockout in mice treated with cisplatin
Comparator: Wild-type (Gadd45a-intact) mice treated with cisplatin

Primary outcomes

Degree of cisplatin-induced hearing loss (auditory function measures); CXCL family protein expression levels in cochlear tissue; Markers of inflammatory pathway activation

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