18 Aug Photodynamic Therapy Can Potentially Target Ovarian Cancer
MedicalResearch: What is the background for this study?
Dr. Taratula: The background for the study consists of previous work we had published in the lab using photodynamic therapy (PDT) as the stand alone treatment modality. We were successful in synthesizing and incorporating the photodynamic nanoplatform in the treatment for ovarian cancer, but our current graduate student, Canan Schumann said he could make the therapy more efficient using his current research on gene therapy. The gene therapy he is currently working on is the delivery of siRNA targeted to the multifaceted oncogenic protein DJ-1 which has been implicated in antioxidative stress defense as well as the overall survival of ovarian cancer. Cancer is highly intelligent able to adapt quickly to new insults that it comes across, even ROS formed inside the cell. Cancer cells can even upregulate a whole host of antioxidant stress response proteins to combat the formation of or scavenge already created ROS. The idea was can we combine our currently used PDT, which uses the generation of reactive oxygen species (ROS) as its cytotoxic mechanism of action, coupled with gene therapy targeted to DJ-1, in hope to drastically increase ROS inside the cell leading to a more pronounced cell death.
MedicalResearch: What are the main findings?
Dr. Taratula: What we found was most surprising. After incubation with our DJ-1 drug delivery system (DDS) and then treatment with our photodynamic compound we saw almost complete tumor eradication in vitro, and just as we hypothesized we also observed a pronounced increase in intracellular ROS in all treatment groups, augmenting PDT’s mechanism of action. We then moved the combinatorial treatment into a mouse animal model an DJ-1 by itself slowed the progression of the tumor but when combined with PDT we observed complete tumor eradication. Unlike the combinatorial treatment group the PDT only group saw tumor regrowth at the end of the study.
MedicalResearch: What should clinicians and patients take away from your report?
Dr. Taratula: With the addition of an intelligently thought out therapeutic modality to a combinatorial regimen one can drastically increase the efficacy of treatment. With this addition you can therefore accomplish two major clinical outcomes:
- 1) alleviating the potential for severe side effects by reducing the need for increased doses of the chemotherapeutic agents being used, therefore increasing patient quality of life
- 2) stopping the regrowth of the cancer after chemotherapy thereby dramatically increasing patient 5 year mortality rates after therapy.
MedicalResearch: What recommendations do you have for future research as a result of this study?
Dr. Taratula: We would like to see the future of this research move into a primary ovarian cancer cell model that is more applicable to a personalized medicinal approach. We have preliminary data showing that the ovarian cancer cell lines that we deal with all have an overexpression of DJ-1 and it has been shown that ovarian cancer relies heavily on DJ-1 for its overall survival and proliferation. By working with primary tumor samples from patients then we can potentially screen and see who might benefit from our gene therapy approach. We are also using the DJ-1 DDS in combination with conventional chemotherapy in hopes to see a similar effect on the proliferation and growth of some of the more aggressive ovarian cancer cell models.
ROS-Induced Nanotherapeutic Approach for Ovarian Cancer Treatment Based on the Combinatorial Effect of Photodynamic Therapy and DJ-1 Gene Suppression
Canan Schumann, Olena Taratula, Oleh Khalimonchuk, Amy L. Palmer, Lauren M. Cronk, Carson V. Jones, Cesar A. Escalante, Oleh Taratula.ROS-Induced Nanotherapeutic Approach for Ovarian Cancer Treatment Based on the Combinatorial Effect of Photodynamic Therapy and DJ-1 Gene Suppression. Nanomedicine: Nanotechnology, Biology and Medicine, 2015; DOI: 10.1016/j.nano.2015.07.005
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Oleh Taratula, PhD (2015). Photodynamic Therapy Can Potentially Target Ovarian Cancer