Gaofeng Fan, PhDAssociate Professor

Ovarian cancer is the leading cause of death from gynecological malignancies and ranks fifth of all cancer-related deaths in women. To date, there is no reliable screening test for the early detection of this“silent”killer disease, and less than 35% of women are diagnosed before Stage III, with five-year survival for Stage III or IV being less than 25%. Improvement in treatment is an urgent need for this devastating disease.
Despite recent advances in surgery, the overall survival from ovarian cancer has not improved significantly for last four decades. Failure in early detection results in disease progression to an advanced stage with metastasis. It has been shown that approximately 70% of patients presents with disease that has spread beyond the ovaries. It is almost impossible to render patients free of disease with surgery due to this diffuse feature. Therefore, our efforts to pinpoint the molecular basis for ovarian carcinoma dissemination and metastasis hold great promise to provide information that will lead to development of next generation chemotherapeutical drugs that can effectively inhibit these events after surgery. 
Another major impediment to successful treatment of ovarian cancer is acquired resistance to therapy. Platinum-based chemotherapeutics combined with Taxol is the conventional treatment for ovarian cancer after surgery. However, no matter how meticulously designed the chemotherapy regimen it is, relapse remains almost inevitable in patients with advanced disease. With the improvement of our understanding of the pathological features of this heterogeneous disease, the concept of targeted therapy has led to a series of pre-clinical and clinical trails, including targeting VEGF, EGF and PDGF signaling, separately or in combination, PARP inhibition in BRCA-deficient context, and inactivation of downstream pathway PI3K-AKT. Encouraging results have been reported, especially for anti-angiogenic and anti-PARP therapies; however, acquired resistance significantly lowers treatment efficacy and still remains as the primary issue to be addressed.
My lab will integrate both biochemical and biological approaches to address these two urgent issues in ovarian cancer treatment. We will also apply high-throughput screen to identify leading compound(s) against novel and druggable target(s) revealed from our studies.