RNA Interference for Antimetastatic Therapy

The suppression of genes involved in tumor progression, metastasis formation, or therapy resistance by RNA interference is a promising tool to treat cancer disease. Efficient delivery of interfering molecules and their sustained presence in tumor cells are required for therapeutic success. This chapter describes a method of systemic application of shRNA expression plasmid via tail vein injection in xenograft mice, causing the sustained reduction of target gene expression in the primary tumor. By choosing S100A4 as a metastasis driving target gene, this therapeutic approach restricted the formation of distant colorectal cancer metastases after intrasplenic transplantation. In vivo imaging of bioluminescent cancer cells allows the monitoring of tumor growth and metastasis formation over time. End point analysis of the trial included scoring of the metastatic burden and the quantification of target gene expression in the tumor. Average S100A4 expression in tumor tissues was reduced by 30 %, causing a 70 % decrease of liver metastases.