US EPA

4532926 

Journal Article 

Therapeutic Strategies against Cyclin E1-Amplified Ovarian Cancers 

Zhang, R 

2017 

For Aim 1, we demonstrated 1)The HSP90-inhibitors 17-AAG and AT13387 has single agent activity against CCNE1-amplifiedcell lines; 2)HSP90-inhibition down regulates homologous recombination (HR) DNA repair and down regulates expression of HR pathway genes; 3)The HSP90-inhibitor AT13387 synergizes with platinum against CCNE1-amplified cell lines. For Aim 2, we demonstrated 1)FOXM1 is necessary for the survival of CCNE1 amplified epithelial ovarian cancer cells.2)FOXM1 interacts with Rb in CCNE1 amplified epithelial ovarian cancer cells. 3)Characterized 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 2)These miRNAs synergize with platinum against CCNE1-amplified cell lines, that is expression of these miRNAs sensitizes cells to platinum.