M.D. Anderson Gynecologic SPORE for Uterine Cancers

MD Anderson癌症中心妇科癌症专门研究项目(SPORT)的总体目标是为预防和治疗子宫癌进行高度创新的转化性研究。这一总体目标包括该计划的以下目标：1)为晚期和复发的子宫内膜癌开发新的治疗策略，2)在包括肥胖妇女在内的高危人群中促进子宫内膜癌的化学预防新策略，以及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，我们建立了一个广度和深度都是无与伦比的高生产率的子宫癌翻译研究社区。该提案包括由经验丰富的翻译科学家领导的4个项目，这些项目展示了高度的翻译影响和突出的科学价值。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”，包括一项针对肥胖、胰岛素抵抗妇女使用二甲双胍的化学预防试验。项目2“使用子宫内膜生物标记物预测晚期疾病”，试图确定在孢子形成的头五年中发现的一组分子生物标记物是否可以解决治疗子宫内膜癌妇女的外科医生面临的特定和重要的临床困境。项目3，“EphA2靶向治疗子宫癌”，重点是一种新的治疗靶点，EphA2。EphA2在相当大比例的子宫癌中过度表达，与总体生存率低有关，并已被证明调节血管生成。该项目将包括一种免疫结合物的Ib期临床试验，该结合物将抗癌治疗与EphA2抗体联系起来。项目4“针对子宫内膜癌中的Pisk信号通路”，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癌发生中的作用。初步数据表明，该途径的多个节点中存在突变，并且根据突变的不同，对途径抑制剂的反应可能不同。该项目将包括一项评估PI3K抑制剂GSK2126458A治疗晚期子宫内膜癌疗效的II期临床试验。四个核心将支持这些项目。核心A(管理核心)、核心B(病理核心)、核心C生物标志物核心和核心D(生物统计和生物信息学核心)。

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).