siRNA-based drug targeting human Bcl-xL against cancers

Abstract

The 2006 discovery of the process of RNA interference opened the door to application of this phenomenon for disease treatments. Short interfering RNA (siRNA) can be used to induce RNA interference, and this approach has generated much interest as a new type of nucleic acid-based drugs in humans and other mammals. However, despite the great potential of siRNA-based drugs in cancer therapy, some drawbacks of siRNAs, such as their instability in vivo and poor cellular uptake, remain unresolved. Here, we review the development of siRNA-based drugs targeting the human Bcl-xL gene, an anti-apoptotic factor overexpressed in many cancers, including prostate cancers. We also introduce a novel application of the biomaterial atelocollagen as a vehicle to functionally deliver tumor-specific siRNA molecules in nude mice. Here, we introduce an orthotopic tumor inoculation model in nude mice: The resulting orthotopic tumors more closely replicate the clinical conditions in humans—including the metastasis mode—than ectopic subcutaneously inoculated tumors.