Endometrial cancer is the most common gynecologic malignancy. Although it is highly treatable in the early stages of disease, therapies for advanced and recurrent disease are rarely curative. A molecular and genetic understanding of endometrial cancer involves the mTOR signaling pathway, an emerging target for treatment of type I disease (the most common presentation). Endometrial cancers show a significant reliance on the mTOR pathway for survival, and studies to date have revealed a clinical advantage in targeting this pathway. Less well developed in the study of endometrial cancer is an understanding of mTOR signaling to its major downstream effector, translational control. Given the poor rate of success for treatment of latestage endometrial cancer, increasing attention is being directed to the development of new therapeutic approaches, including targeting the mTOR pathway. Here, we discuss the potential benefit of targeting mTOR combined with existing chemotherapies by monitoring its impact on translational regulatory pathways and key translation targets in endometrial cancer. We also highlight laboratory and clinical research findings that will provide new avenues for future research and clinical development. Clin Cancer Res; 17(24); 7518-28. Ó2011 AACR.

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e15548 Background: The majority of endometrial cancers present as early stage tumors, yet those that are advanced at diagnosis are associated with poor outcomes. The role of radical debulking surgery for endometrial cancer is not clear. However, the use of neoadjuvant chemotherapy is also unproven. We sought to evaluate if utilizing neoadjuvant chemotherapy for advanced endometrial cancer affected outcomes. Methods: A retrospective review from two hospitals served by one academic center from 2002 to 2011 was performed. All patients with stage 3 or 4 disease were identified. Patients with non-epithelial cell types, including carcinosarcoma, were excluded. Patients who received neoadjuvant treatment prior to surgery were identified. A case-control design was utilized matching patients 1:3 or 1:4 stratified by age, stage, grade, histology and performance status. Descriptive statistics and nonparametric analyses were utilized. Results: A total of 115 patients with advanced endometrial cancer were identified. 19 were excluded due to wrong cell type and 1 due to stage 3 disease based on positive cytology. 6 patients had a neoadjuvant treatment approach (NAs). 20 patients were identified as matched controls (CTRLs). The average age was 61 for the NAs, and 63 for the CTRLs. The average BMI was 26.9 for the NAs, and 27.4 for the CTRLs. NAs were more likely to have stage 4 disease—5/6 NAs versus 5/20 CTRLs. Both groups had a high proportion of grade 3 tumors—4/6 NAs versus 15/20 CTRLs. The performance status was similar in both groups. The median number of chemotherapy cycles was 11 in the NAs, and 4 in the CTRLs. 18/20 CTRLs received adjuvant treatment, and 17 included systemic chemotherapy. In the NAs, with a median follow-up of 17 months, 4 were alive with disease (AWD) and 2 were dead of disease (DOD). In the CTRLs, with a median follow-up of 14 months, 7 patients were NED, 8 were AWD, and 5 were DOD. Conclusions: Despite a small sample size, our results indicate that primary surgery remains the preferred strategy for patients with advanced endometrial cancer. However, prospective data is needed to determine to what extent neoadjuvant chemotherapy affects outcomes.