Targeting Noncanonical Nuclear Factor Kappa B Signaling in CYLD Cutaneous Syndrome by Selective Inhibition of IκB Kinase Alpha

    June 2026 in “ Strathprints: The University of Strathclyde institutional repository (University of Strathclyde) ”
    Kirsty Hodgson, Joseph Inns, Gary Reynolds, Emily Stephenson, Andrew Paul, Naomi Sinclair, Giacomo Berretta, Christopher P. Lawson, Andrew M. Frey, Iglika G. Ivanova, Éva Ádám, Christopher J. Lord, Simon Cockell, Jonathan Coxhead, Nikoletta Nagy, David Adams, Márta Széll, Matthias Trost, Muzlifah Haniffa, Simon P. Mackay, Neil D. Perkins, Neil Rajan
    TLDR Topical IKKα inhibitors may help prevent CCS tumours.
    The study investigates NF-κB signalling in CYLD cutaneous syndrome (CCS) tumours to identify potential drug targets. Researchers used transcriptomics, proteomics, and single-cell RNA sequencing on patient-derived CCS tumour cells, revealing evidence of non-canonical NF-κB signalling with increased p100 to p52 processing and RelB protein expression. IκB kinase alpha (IKKα) was identified as a candidate target, and a novel IKKα inhibitor (SU1644) was tested on CCS tumour spheroid cultures, showing reduced tumour viability. The findings support the potential use of topical IKKα inhibitors as a preventive treatment for CCS.
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