Development of km23-Based Diagnostics and Therapeutics

摘要

Similar to other solid tumors, ovarian cancers are resistant to the growth inhibitory effects of the natural epithelial growth inhibitor TGF, suggesting that alterations in TGF Beta pathways contribute to ovarian cancer progression. The TGF Beta resistance is frequent, perhaps exceeding 75% of cases, especially for recurrent ovarian cancers. Despite the high frequency of TOF3 resistance that occurs in ovarian cancers, thus far, no clinically useful agents, which target the signaling pathways of any of the TGF Beta superfamily members, have been developed for this disease. Accordingly, there is a great need to develop TGF Beta-based agents and indicators for the diagnosis, therapy, and prognosis of ovarian cancer. Further, TGF Beta and some of its signaling components can function as tumor suppressors. We have identified a novel TGF Beta signaling component (km23) that is altered in 42% of ovarian cancer patient tumors. Our results suggest that the growth inhibitory effects of km23 may be lost in human ovarian cancers expressing altered forms of km23; km23 may normally function as a tumor suppressor. Our studies are likely to lead to significant new information regarding the development and progression of ovarian cancer, and to the development of novel diagnostics and therapeutics for this disease.