Understanding the Molecular Basis of Chemoresistance in Ovarian Cancer

Ovarian cancer is the number one cause of gynecologic cancer deaths in the United States as well as the fifth leading cause of cancer-related death in women. Epithelial ovarian cancer accounts for 85% to 90% of all cancers of the ovaries and is treated with chemotherapy drugs such as cisplatin and carboplatin. In many cases of recurring ovarian cancers, chemoresistance is acquired through poorly understood mechanisms involving DNA organization and repair. This study aimed to elucidate characteristics of DNA that lead to chemoresistance in ovarian cancer. Molecular comparisons of chemoresistant and chemo-sensitive cell lines, SKOV3 and A2780, using the modified alkaline comet assay revealed inherent differences in crosslink formation and DNA damage in resistant cells. In addition, Liquid Chromatography Mass Spectrometry (LC/MS) revealed numerous proteins unique to each cell type that function in mRNA preparation, protein biosynthesis, and cytoskeletal organization. These data suggest the potential role of several key proteins in the formation of resistance, and highlight the need to further test the pathways involved in chemoresistance. Furthermore, characteristics such as crosslink formation and the presence of distinct proteins may serve as a biomarker for chemoresistance in ovarian cancer