Radioresistance markedly impairs the efficacy of cancer therapy and involves anti-apoptotic signal transduction pathways that prevent the treatment-induced cell death.Anti-apoptotic proteins such as Bcl-xL, Bcl-2, Mcl-1, and inhibitors of apoptosis proteins (IAP), are overexpressed in prostate cancer and contribute to tumor initiation, progression and resistance to therapy.They are highly attractive molecular targets for the development of novel anti-cancer therapy to overcome radiation resistance.Using nanoparticle-based, tumor-targeted delivery of siRNAs against Bcl-2 and Mcl-1, we demonstrated that Bcl-2 and Mcl-1 knockdown radiosensitized human prostate and pancreatic cancer xenografts in nude mice.