Martin Cannon, PhD
- University of Arkansas for Medical Science
Dendritic cell vaccination & inhibition of tumor-associated immune suppression
Recent clinical studies have found that ovarian cancer patients with Th17 lymphocyte infiltrates in tumors enjoy a markedly longer overall survival, suggesting that Th17 cells play a protective role against ovarian cancer. Dr. Cannon designed an innovative approach to dendritic cell vaccination that activates a Th17 T cell response against ovarian cancer, raising the exciting prospect of dendritic cell vaccine clinical trials to stimulate Th17 immunity. However, ovarian tumor associated myeloid cells suppress anti-tumor immunity stimulated by dendritic cells. This project will determine the mechanisms of immune suppression and test drugs that have the potential to alleviate suppression and boost the efficiency of dendritic cell vaccination.
Carol Hanchette, PhD
- University of Louisville
Ovarian Cancer and Pulp and Paper Manufacturing in the US: A Geospatial Analysis
The primary aim of Dr. Hanchette‘s project is to discover whether high rates of ovarian cancer occurrence in the United States correspond with the locations of pulp and paper mills. An association between the two has been reported, using state rates, and is of concern because of the effluents released by the industry. She plans to explore this potential ovarian cancer-paper mill relationship using smaller units of geography, such as counties, which would provide a better approximation of exposure. Dr. Hanchette will use geographic information system (GIS) software for mapping, visualization, spatial statistics, and environmental modeling of pollutants.
Stephen Howell, MD
- University of California San Diego
Dendrimer-folate targeting of paclitaxel to ovarian cancer
Paclitaxel is used extensively for the treatment of ovarian cancer. The overall goal of this project is to test the efficacy and toxicity of a novel paclitaxel drug delivery system, capable of selectively targeting ovarian cancers and thereby increasing tumor cell kill without enhancing toxicity. Dr. Howell has developed a unique dendrimer that can carry paclitaxel and can be loaded with folates so that it binds very tightly to the folate receptors that are present in large amounts in most ovarian cancers, thus increasing the amount of drug that gets into the tumor.
Mythreye Karthikeyan, PhD
- University of South Carolina
Specific targeting of Inhibin in ovarian cancers lacking the Type-III TGF-β receptor
Ovarian cancer is associated with a high degree of heterogeneity (meaning the tumors differ from patient to patient), highlighting the importance of developing individualized treatment. Changes in the levels of the growth factors belonging to the Transforming Growth Factor (TGF-β) family, specifically Inhibin, are frequently found in ovarian cancer. In addition, loss of the receptor for Inhibin on the surface of ovarian cancer cells, namely Type III TGF-β receptor, is also frequently observed. The goal of Dr. Karthikeyan‘s project is to evaluate the pre-clinical feasibility of specifically targeting Inhibin so that it will interact with one class of receptors and not another in order to prevent Inhibin‘s ability to promote tumor growth and metastasis, thereby improving personalized treatment strategies for ovarian cancer.
Peter Kuhn, PhD
- University of Southern California
Single-cell molecular profiling of biopsies of epithelial cancer
Next-generation sequencing of single cancer cells identified from the blood of ovarian cancer patients can potentially guide treatment decisions, identify recurrence early, and lead to earlier and more accurate diagnosis of the disease. Dr. Kuhn will use a “fluid biopsy” to extract rare tumor cells (also known as circulating tumor cells or CTCs) that travel in the blood far away from the main tumor. He will obtain genetic information from cells captured at multiple time points over the course of the disease to investigate if certain genetic markers correspond to the patient‘s cancer status. This will lay the foundation for guiding treatment decision at every clinical visit.
Steffan Nawrocki, PhD
- University of Texas Health Science Center at San Antonio
A new strategy to overcome drug resistance in ovarian cancer
Platinum-based chemotherapy is prevalently used for the treatment of ovarian cancer. The prognosis for patients with platinum-resistant ovarian cancer is extremely poor, and new treatments for this disease are urgently needed. Dr. Nawrocki‘s preliminary data indicate that protein degradation may be an essential process that is required for resistance to platinum-chemotherapy as its inhibition reverses cisplatin resistance in ovarian cancer models. The goal of this project is to define the mechanisms by which protein degradation regulates chemosensitivity. He hypothesizes that protein turnover is required for the development of resistance to platinum chemotherapy and that it can be targeted to improve overall survival.
Kwong-Kwok Wong, PhD
- University of Texas MD Anderson Cancer Center
Targeted Therapy for Ovarian Clear Cell Carcinoma
Patients with late stage clear cell ovarian carcinoma have poorer survival rates than the more common high-grade serous ovarian carcinomas. Current therapies are not effective for this aggressive cancer. Dr. Wong‘s preliminary data suggests that targeting the mTOR pathway, which is frequently activated in cancers and also implicated in cell growth, protein synthesis, invasion, and cell metabolism, is a promising strategy to treat clear cell ovarian carcinomas. He hypothesizes that it will be more effective to kill the cancer cells if both the mTOR and c-Myc pathways are targeted. In this project, he will use a pre-clinical mouse model to investigate the efficacy of combining two inhibitors, one for each pathway, in treating clear cell ovarian carcinoma.
Bin Zhang, MD, PhD
- Northwestern University
Treating ovarian cancer with novel ecto-5’nucleotidase (CD73) inhibitors
Tumors have elaborate suppressive mechanisms against host immune system to enhance their survival. Ovarian tumors highly express a protein called CD73 that limits anti-tumor immune response in order to promote tumor growth. Dr. Zhang‘s recent research demonstrates that CD73 may serve as an emerging immune target for ovarian cancer treatment. In this project, he will evaluate the efficacy of CD73 blockade with an FDA-approved drug as a novel means to enhance ovarian cancer immunotherapy. He hopes open the door for the rapid translation of these preclinical findings into the clinic for effective ovarian cancer treatment.