231 A Novel siRNA Screening Approach for Target Identification in Oncology: Focus On Purinome Enzymes

Results: Effective down-regulation of TS resulted in increased in vitro cell growth inhibition effect of PMX. The combined treatment of DFP-10825 and PMX achieved superior tumor growth suppression in a MSTO-211H xenograft model, compared to each single treatment. DFP-10825 was cooperated with PMX to induction of apoptosis as a result of decreasing TS expression. In addition, PMX tended to suppress immunological responses induced by shRNA in DFP-10825. Conclusion: Despite the improvement in diagnosis and treatment, MPM and NSCLC patients still have a dismal prognosis. To improve the response to chemotherapy, new biologic agent should be introduced. Our results suggest that our tumor targeted anti-thymidylate synthase (TS) RNAi system, DFP-10825, would be a new biologic agent to extend clinical utility of PMX and achieve higher clinical results than supportive care in patients with MPM and NSCLC.