M.D. Anderson Gynecologic SPORE for Uterine Cancers

MD安德森癌症中心妇科癌症卓越研究专业项目（SPORE）的总体目标是在子宫癌的预防和治疗方面进行高度创新的转化研究。这一总体目标包括以下目标：1)开发晚期和复发子宫内膜癌的新治疗策略；2)在包括肥胖妇女在内的高危人群中促进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，我们建立了一个在广度和深度上无与伦比的高产子宫癌转化研究社区。本提案包括4个具有较高转化影响力和突出科学价值的项目，由经验丰富的转化科学家领导。项目1，“二甲双胍用于肥胖、胰岛素抵抗女性子宫内膜癌的化学预防”，包括一项使用二甲双胍治疗肥胖、胰岛素抵抗女性的化学预防试验。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的前五年发现的一组分子生物标志物是否可以解决治疗子宫内膜癌女性的外科医生面临的一个特殊而重要的临床困境。项目3“EphA2靶向治疗子宫癌”，重点研究新的治疗靶点EphA2。EphA2在很大比例的子宫癌中过度表达，与较差的总生存率相关，并已被证明可调节血管生成。该项目将包括一种免疫偶联物的Ib期临床试验，该偶联物将抗癌治疗药物与针对EphA2的抗体联系起来。项目4“targeted the PISK Signaling Pathway in endome内膜癌”，重点研究磷脂酰肌醇-3激酶PI3K/PTEN/AKT/mT0R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，并且对途径抑制剂的反应可能因突变而异。该项目将包括一项II期临床试验，评估PI3K抑制剂GSK2126458A在晚期子宫内膜癌中的疗效。Four Cores将支持这些项目。核心A（行政核心），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).