Modulators of Response to Tumor Necrosis-related Apoptosis Inducing Ligand (TRAIL) Therapy in Ovarian Cancer

摘要

Ovarian cancer is the leading cause of death from gynecologic cancers in the developed world. We have previously identified a homeobox gene, Six1, which is overexpressed in ovarian cancers as compared to normal ovarian surface epithelium. We have shown that overexpression of Six1 is associated with resistance to Tumor Necrosis Factor-related Apoptosis Inducing Ligand (TRAIL) based therapies, both in cell culture and in patient tumors. We also have discovered that elevated Six1 is associated with tumor formation in mice and that the TRAIL decoy receptor DcR2 is overexpressed when Six1 is overexpressed. However, knockdown of DcR2 does not restore TRAIL sensitivity to Six1 overexpressing tumors, implying additional mechanisms. On-going studies are evaluating the mechanism and significance of these findings on the way to designing new treatments for ovarian cancer.