Inhibition of the Mevalonate Pathway Targets Neuroblastoma Stem Cells

Introduction: High-risk neuroblastoma is a difficult-to-treat cancer with high rates of recurrence and treatment resistance, likely driven by a population of cancer stem cells. Multiple previous studies have suggested that the use of mevalonate pathway inhibitors, such as statins and bisphosphonates, may have anticancer activity against high-risk tumors. Methods: We aimed to observe the use of mevalonate pathway inhibitors against the cancer stem cell population of high-risk neuroblastoma cell lines SH-SY5Y, SK-N-AS, and SK-N-BE(2)-C using spheroid-based assays. Results: We observed significant reductions in spheroid formation capability, stem cell frequency, and stemness properties of these neuroblastoma cancer stem cells with fluvastatin and zoledronate treatment. Conclusion: Treatment with mevalonate pathway inhibitors leads to reduced neuroblastoma cancer stem cell function through reductions in protein geranylgeranylation.