| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Research Abstract |
Ovarian cancer remains the most lethal gynecologic malignancy, largely due to the lack of effective chemotherapeutic agents in the se tting of platinum resistant disease. Chemotherapeutic agents targeting critical molecular pathways hold promise for improving survival in these patients. Understanding the critical molecular pathways is central to the development of such agents. With digital karyotyping, we discovered a new amplified oncogene, NAC1. A subsequent clinicopathological and molecular biological analysis of NAC1 suggested that NAC1 could be a potential molecular target in ovarian cancer. Repression of NAC1 induced apoptosis of ovarian cancer cells. Overexpression of NAC1 in cells lacking endogenous NAC1 results in taxane resistance. NAC1 Knock down of NAC1 in taxane resistant ovarian cancer cell lines restores taxane sensitivity. NAC1 dimerization is integral to its function. Base d on the structural analysis of the NAC1 BTB domain, we screened candidate inhibitors of NAC1 dimer formation. We have begun development on a carcinogenic mouse model of NAC1 in which inhibitors will be tested prior to being introduced in the clinical setting.
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