Folate Targeted Delivery of a CDKI

DESCRIPTION (provided by applicant): Ovarian cancer is the second most common gynecological malignancy and is the fourth leading cause of cancer mortality in women. Ovarian cancer is the second most common gynecological malignancy and is the fourth leading cause of cancer mortality in women. Nationwide 23,400 new cases will be diagnosed in 2002 and 13,900 women will die of ovarian cancer. Only 25% of all cases are detected at an early stage (American Cancer Society, 2002). Seventy five percent of patients with ovarian cancer present with advanced disease and less than 40% survive 5 years. These results have improved only slightly over the last four decades and new treatment modalities are needed to impact this disease. Our long-term goal is to improve the survival rate of women who have ovarian cancer. Our objective in this application is to use folate to target a cell growth inhibitor to tumor cells in an ovarian cancer model system. Our hypothesis is that folate-targeted liposomes containing a stabilized version of the cyclin dependent kinase inhibitor, p27Kip1, will block tumor cell growth in vivo. The rationale for the proposed studies is that an effective therapy for the treatment of ovarian cancer found in the peritoneal cavity of women with advanced ovarian cancer will increase the survival rate of women with ovarian cancer. Our research team is uniquely suited to undertake this proposal. The small business, Endocyte, is a leader is the field of folate-targeted liposome gene delivery. The academic investigators bring knowledge and experience in the mechanistic basis of p27Kip1's control of tumor cell growth along with access to an imaging facility core for monitoring in vivo tumor cell growth. To test our hypothesis, the following specific aims are proposed: Aim 1: Analyze folate-targeted liposome delivery of p27Kip1 into cultured tumorigenic cell lines. Aim 2: Evaluate tumor progression after folate/liposome/p27Kip1 treatment in an ovarian cancer model system and Aim 3. Analyze tumor growth after folate/liposomelp27Kip1 treatment using in vivo imaging technology.