1. Signaling Pathways Produced By Combining DsRNA with Paclitaxal to treat Ovarian Cancer Switu Patel

2. Ovarian Cancer Fifth in, malignant deaths of US women Cause unknown Common Therapy: surgery + chemotherapy

3. Dual treatments In Van et al. they combined Double stranded RNA (DsRNA) with therapeutic agents like paclitaxel and carboplatin to get a significant decrease in cell viability DsRNA is known to stop the immunosuppression signals caused by ovarian tumor cells and activate four innate immune receptors

4. Cell response to dsRNA When stimulated within a cell, it activates four receptors.

5. Cell response to dsRNA DsRNA activates Protein Kinase and gives it a pro-apoptotic or cell killing response

6. Cell response to dsRNA Which then phosphorylates EIF2S which stops translation

7. Cell response to dsRNA Apoptosis PKR also activates FADD which further activates caspase 8

8. Cell response to dsRNA Apoptosis Other pathways that influence apoptosis

9. Individual vs. Combined treatments

11. Proposal question What essential pathways related to apoptosis are activated by dsRNA + paclitaxel? ◦ These pathways will serve as biomarkers for individual patients

12. Experiment Apoptotic PCR Array For: ◦ Untreated ◦ Treated: dsRNA, paclitaxel, dsRNA + paclitaxel

14. Hypothetical Results Caspase 3

15. Results We expect that the samples treated with combined therapeutic agents will have a higher levels of apoptotic pathway molecules or lower CT values, than the individual treated samples. However, it may cause down regulation of anti-apoptotic proteins or cause up regulation of pro-apoptotic or cell death proteins.