The Wistar Institute of Anatomy and Biology Philadelphia United States
For Aim 1, we demonstrated 1The HSP90-inhibitors 17-AAG and AT13387 has single agent activity against CCNE1-amplifiedcell lines 2HSP90-inhibition down regulates homologous recombination HR DNA repair and down regulates expression of HR pathway genes 3The HSP90-inhibitor AT13387 synergizes with platinum against CCNE1-amplified cell lines. For Aim 2, we demonstrated 1FOXM1 is necessary for the survival of CCNE1 amplified epithelial ovarian cancer cells.2FOXM1 interacts with Rb in CCNE1 amplified epithelial ovarian cancer cells. 3Characterized small molecule inhibitor that disrupts the interaction between FOXM1 and Rb in CCNE1 amplified epithelial ovarian cancer cells. For Aim 3, we demonstrated 1 Certain miRNAs including miR-1255b, miR-148b, and miR-193b inhibit HR DNA repair 2These miRNAs synergize with platinum against CCNE1-amplified cell lines, that is expression of these miRNAs sensitizes cells to platinum.