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Signaling Pathways Produced
By Combining DsRNA with
Paclitaxal to treat Ovarian
Cancer
Switu Patel
Ovarian Cancer
Fifth in, malignant deaths of US women
 Cause unknown
 Common Therapy: surgery +
chemotherapy

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

Cell response to dsRNA
When stimulated within a cell, it activates
four receptors.
Cell response to dsRNA
DsRNA activates Protein Kinase and gives it a pro-apoptotic
or cell killing response
Cell response to dsRNA
Which then phosphorylates EIF2S which stops translation
Cell response to dsRNA
PKR also activates FADD which
further activates caspase 8
Apoptosis
Cell response to dsRNA
Other pathways that influence
apoptosis
Apoptosis
Individual vs. Combined treatments
Proposal question

What essential pathways related to apoptosis
are activated by dsRNA + paclitaxel?
◦ These pathways will serve as biomarkers for
individual patients
Experiment
Apoptotic PCR Array
 For:

◦ Untreated
◦ Treated: dsRNA, paclitaxel, dsRNA + paclitaxel
Hypothetical Results
Caspase 3
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.
