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.