Epithelial ovarian cancer is the most frequent cause of gynecologic malignancy-related mortality in women in the United States. Over the past 30 years standard treatments for newly diagnosed ovarian cancer have consisted of cytoreductive surgery followed by platinum-taxane chemotherapy. After initial chemotherapy, the majority of women with ovarian cancer will have a relapse of their disease and require additional treatment. Recently, limited targeted-therapy options, such as PARPis, have been approved to treat ovarian cancer. However, the greatest clinical benefit from PARPi therapy has mainly been observed in patients with homologous recombination (HR) deficiency. Moreover, tumors initially HR-deficient commonly acquire HR-proficiency after PARPi treatment by restoration of HR function, thereby becoming resistant to PARPis. Therefore, there is an urgent unmet medical need to develop alternative therapeutic strategies for patients with ovarian cancer. A growing emphasis in ovarian cancer drug discovery efforts has been on targeting chromatin modifiers (i.e., chromatin-remodeling enzymes and histone-modifying enzymes). Challenges in target identification and characterization have resulted in a narrow focus on the development of epi-drugs for ovarian cancer therapy. We hypothesize that combination of chemical/genetic screen and multidimensional profiles of genome, functionome, and druggome can identify novel epi-drug targets and combinations for ovarian cancer treatment.
This grant was made possible in part by a generous donation by the Melitta S. and Joan M. Pick Charitable Trust.
Dr. Xiaowen Hu is currently a research resistant professor in Department of Obstetrics and Gynecology at University of Pennsylvania. Dr. Hu got her B.S. degree in biology from Sichuan University, China and received her Ph.D. from Shanghai Institutes for Biological Sciences of Chinese Academy of Sciences. Dr. Hu focused on the field of ovarian cancer research since she was a Ph.D. student. During her postdoc training at the Ovarian Cancer Research Center of University of Pennsylvania, Dr. Hu started exploring the genomics, epigenetics and no-coding genome of ovarian cancer. Her current research interest largely focused on the integration of cancer genome, epigenome, and computational biology, and then developing targeted therapy for ovarian cancer, especially, targeting the epigenetic modulators that significantly altered during ovarian cancer development and progression. Dr. Hu’s research has been supported by the Foundation for Women’s Cancer and Ovarian Cancer Research Fund Alliance. She is a previous recipient of Ann and Sol Schreiber Mentored Investigator Award from the Ovarian Cancer Research Fund.