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Hedgehog pathway inhibitors (HHIs), specifically sonidegib and vismodegib, have expanded treatment options for advanced basal cell carcinoma (BCC) but are associated with adverse events (AEs) such as muscle spasms, creatine phosphokinase increase, alopecia, and dysgeusia. These AEs often occur early in treatment and can lead to discontinuation, impacting clinical outcomes. Differences in pharmacokinetics between the two drugs may affect the timing and resolution of AEs. Effective management strategies, including treatment interruptions, dose reductions, and both nonpharmacologic and pharmacologic interventions, can help manage AEs while maintaining disease control. Awareness and planning are crucial for healthcare providers and patients to optimize therapeutic responses and avoid discontinuation.

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.