Signaling Pathways Signaling Pathways Produced By Combining Produced By Combining DsRNA with Paclitaxal to DsRNA with Paclitaxal to treat Ovarian Cancertreat Ovarian Cancer

Switu Patel

Ovarian CancerOvarian CancerFifth in, malignant deaths of US

womenCause unknownCommon Therapy: surgery +

chemotherapy

Dual treatmentsDual treatmentsIn 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

Cell response to dsRNACell response to dsRNA

When stimulated within a cell, it activates four receptors.

Cell response to dsRNACell response to dsRNA

DsRNA activates Protein Kinase and gives it a pro-apoptotic or cell killing response

Cell response to dsRNACell response to dsRNA

Which then phosphorylates EIF2S which stops translation

Cell response to dsRNACell response to dsRNA

Apoptosis

PKR also activates FADD which further activates caspase 8

Cell response to dsRNACell response to dsRNA

ApoptosisOther pathways that influence apoptosis

Individual vs. Combined Individual vs. Combined treatmentstreatments

Proposal questionProposal questionWhat essential pathways related to

apoptosis are activated by dsRNA + paclitaxel? ◦These pathways will serve as biomarkers

for individual patients

ExperimentExperimentApoptotic PCR ArrayFor:

◦Untreated◦Treated: dsRNA, paclitaxel, dsRNA +

paclitaxel

Hypothetical ResultsHypothetical Results

Caspase 3

ResultsResultsWe 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.