The abstract is read at the publisher; the summary is JClub's.
Ruxolitinib exposure is linked to aggressive cutaneous squamous cell carcinoma (cSCC) in pharmacovigilance and a large cohort, with mechanistic support from JAK2-driven MAPK activation.
- Why it matters: Secondary skin cancers are a major feared adverse effect of cancer therapies, but the cutaneous oncogenic risk and signaling basis for ruxolitinib were unclear.
- What they did: The study combined international pharmacovigilance analysis with a large cohort, then tested causality in vitro and in vivo; phosphoproteomics identified COT kinase–mediated alternative MAPK activation, validated by chemical inhibition and COT impairment.
- The result: COT impairment rescued ruxolitinib’s pro-oncogenic effects, and integrated epidemiological, in vitro, and in vivo evidence suggested ruxolitinib also increases melanoma risk.
The findingWhy it mattersWhat they didThe result
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