Clear cell carcinoma (CCC) of the ovary is known to show poorer sensitivity to chemotherapeutic agents and to be associated with a worse prognosis than the more common serous adenocarcinoma or endometrioid adenocarcinoma. To improve the survival of patients with ovarian CCC, the deeper understanding of the mechanism of CCC carcinogenesis as well as the efforts to develop novel treatment strategies in the setting of both front-line treatment and salvage treatment for recurrent disease are needed. In this presentation, we first summarize the mechanism responsible for carcinogenesis. Then, we highlight the promising therapeutic targets in ovarian CCC and provide information on the novel agents which inhibit these molecular targets. Moreover, we discuss on the cytotoxic anti-cancer agents that can be best combined with targeted agents in the treatment of ovarian CCC.
Adenocarcinoma, Clear Cell/drug therapy/*etiology/metabolism ; Antineoplastic Agents/therapeutic use ; Female ; Forecasting ; Humans ; Neoplasm Recurrence, Local/prevention & control ; Ovarian Neoplasms/drug therapy/*etiology/metabolism

PURPOSE: It is known that cyclooxygenase (COX)-2 expression is increased in Barrett's esophagus and esophageal adenocarcinomas. We studied COX-2 expression and the effect sulindac has on the genesis of Barrett's esophagus and adenocarcinoma in rats undergoing esophagogastroduodenal anastomosis (EGDA). MATERIALS AND METHODS: Fifty-one rats were divided into a control group (n=27), a 500ppm sulindac-treated group (n=15) and 1000 ppm sulindac-treated group (n=9). Randomly selected rats were killed by diethyl ether inhalation at 20 and 40 weeks after surgery. RESULTS: At 40 weeks, rats treated with 1000 ppm sulindac showed narrower esophageal diameter and milder inflammation than the control rats. At 40 weeks, the incidence of Barrett's esophagus was similar between control and sulindac-treated groups, but the incidence of adenocarcinoma was significantly lower in the 1000ppm sulindac-treated group than either the control or 500 ppm sulindac-treated groups. COX-2 was significantly increased in the lower esophagus of control rats killed at 40 weeks. Cyclin D1 expression was negligible in the sulindac- treated group compared with the control group. CONCLUSION: We suggest that the chemopreventive effect of sulindac is related to decreased COX-2 and cyclin D1 expression, which may be influenced by reduced inflammation.
Adenocarcinoma/etiology/metabolism/*prevention & control ; Animals ; Antineoplastic Agents/therapeutic use ; Barrett Esophagus/etiology/metabolism/prevention & control ; Blotting, Western ; Cyclin D1/metabolism ; Cyclooxygenase 2/metabolism ; Duodenogastric Reflux/*complications ; Esophageal Neoplasms/etiology/metabolism/*prevention & control ; Immunohistochemistry ; Male ; Proliferating Cell Nuclear Antigen/metabolism ; Rats ; Rats, Sprague-Dawley ; Sulindac/*therapeutic use