M.D. Anderson Gynecologic SPORE for Uterine Cancers

MD安德森癌症中心的妇科癌症专业卓越研究计划（SPORE）的总体目标是为预防和治疗子宫癌进行高度创新的转化研究。该计划的总体目标包括以下目标：1）为晚期和复发性子宫内膜癌开发新的治疗策略，2）促进高危人群（包括肥胖妇女）子宫内膜癌化学预防的新策略，3）将分子诊断纳入临床决策。在过去的5年里，作为唯一的子宫癌孢子，我们建立了一个高度生产性的子宫癌转化研究社区，在广度和深度上都是无与伦比的。该提案包括4个项目，由经验丰富的翻译科学家领导，具有高度的翻译影响力和杰出的科学价值。项目1，“二甲双胍用于肥胖、胰岛素抵抗妇女子宫内膜癌的化学预防”，包括一项使用二甲双胍治疗肥胖、胰岛素抵抗妇女的化学预防试验。项目2，“使用子宫内膜生物标志物预测晚期疾病”，旨在确定在SPORE的前五年中发现的一组分子生物标志物是否可以解决外科医生护理子宫内膜癌妇女所面临的特定和重要的临床困境。项目3，“EphA 2在子宫癌中的靶向作用”，专注于一种新的治疗靶点EphA 2。EphA 2在相当大比例的子宫癌中过表达，与较差的总体存活率相关，并且已显示出调节血管生成。该项目将包括将抗癌治疗剂与针对EphA 2的抗体连接的免疫缀合物的Ib期临床试验。项目4“靶向子宫内膜癌中的PISK信号通路”，重点关注磷脂酰肌醇-3-激酶PI 3 K/PTEN/AKT/mT 0 R信号通路在子宫内膜肿瘤发生中的作用。初步数据表明，突变存在于该途径的多个节点中，并且对途径抑制剂的反应性可能基于突变而不同。该项目将包括一项II期临床试验，评估PI 3 K抑制剂GSK 2126458 A在晚期子宫内膜癌中的疗效。四个核心将支持这些项目。核心A（管理核心）、核心B（病理学核心）、核心C生物标志物核心和核心D（生物统计学和生物信息学核心）。

The overall goal of the Gynecologic Cancer Specialized Program of Research Excellence (SPORE) at MD Anderson Cancer Center is to conduct highly innovative translational research for the prevention and treatment of uterine cancers. Encompassed within this overall goal are the following goals of the program: 1) to develop novel therapeutic strategies for advanced and recurrent endometrial cancer, 2) to promote novel strategies for chemoprevention of endometrial cancer in high risk cohorts, including obese women, and 3) to incorporate molecular diagnostics into clinical decision-making. Over the last 5 years, as the only Uterine Cancer SPORE, we established a highly productive uterine cancer translational research community that is unparalleled in breadth and depth. This Proposal includes 4 Projects that display high translational impact and outstanding scientific merit, led by experienced translational scientists. Project 1, "Metformin for the Chemoprevention of Endometrial Cancer in Obese, Insulin-Resistant Women," includes a chemoprevention trial using metformin for obese, insulin-resistant women. Project 2, "Use of Endometrial Biomarkers for Prediction of Advanced Disease," seeks to determine if a panel of molecular biomarkers discovered during the first five years of the SPORE can address a specific and important clinical dilemma facing surgeons caring for women with endometrial cancer. Project 3, "EphA2 Targeting in Uterine Carcinoma," focuses on a novel therapeutic target, EphA2. EphA2 is overexpressed in a substantial proportion of uterine cancers, is associated with poor overall survival, and has been shown to regulate angiogenesis. This project will include a phase Ib clinical trial of an immunoconjugate that links an anti-cancer therapeutic to an antibody against EphA2. Project 4 "Targeting the PISK Signaling Pathway in Endometrial Carcinoma," focuses on the role of the phosphatidylinositol-3-kinase PI3K/PTEN/AKT/mT0R signaling pathway in endometrial tumorigenesis. Preliminary data suggests that mutations exist in multiple nodes of this pathway, and that responsiveness to pathway inhibitors may differ based on mutation. This project will include a phase II clinical trial assessing the efficacy of the PI3K inhibitor, GSK2126458A, in advanced endometrial carcinoma. Four Cores will support these projects. Core A (Administrative Core), Core B (Pathology Core), Core C Biomarkers Core, and Core D (Biostatistics and Bioinformatics Core).