Tecan Industry Spotlight: Timing Matters: Statins as a Repurposing Strategy for Fighting Aggressive Squamous Cell Carcinoma

Cutaneous squamous cell carcinoma (SCC) is a primary driver of mortality in patients with recessive dystrophic epidermolysis bullosa (RDEB), necessitating the discovery of safe, effective systemic or topical therapies. Using transcriptome-guided drug repurposing, we identified statins as a potential therapeutic intervention for RDEB-associated SCC. In vitro, lovastatin exhibited significant cytostatic effects and induced caspase-dependent apoptosis. This effect was rescued by mevalonate and geranylgeraniol, confirming on-target inhibition of the mevalonate pathway. While topical application of lovastatin in an in vivo xenograft model resulted in significant reduction in tumor growth, we could observe that its efficacy was limited by rapid clearance from the tumor and the induction of compensatory feedback mechanisms. Our findings suggest that while the established safety profile of statins makes them highly attractive candidates for repurposing, clinical success will depend on overcoming two critical barriers: establishing dosing regimens that maintain therapeutic levels below the threshold of local toxicity and developing strategies to circumvent secondary feedback loops.