M.D. Anderson Gynecologic SPORE for Uterine Cancers

M.D. Anderson 妇科孢子治疗子宫癌

• 批准号: 8321100
• 负责人: Karen Hsieh Lu
• 金额: $ 230万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-14 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8321100
• 关键词: 1-Phosphatidylinositol 3-Kinase; Address; Adult; Antibodies; Bioinformatics; Biological; Biological Markers; Biological Models; Biometry; Biopsy; Cancer Center; Cancer Patient; Carcinoma; Caring; Cetuximab; Chemoprevention; Chemopreventive Agent; Clinical; Clinical Research; Clinical Trials; Colorectal Cancer; Communities; Data; Development; Diagnosis; Diagnostic; Disease; Doctor of Medicine; Effectiveness; Endometrial; Endometrial Carcinoma; Epidemic; Formalin; Foundations; Goals; Growth; Gynecologic; Histocompatibility Testing; Human; Immunoconjugates; Incidence; Insulin Resistance; KRAS2 gene; Laboratories; Link; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of lung; Metformin; Modeling; Molecular; Monoclonal Antibodies; Mutation; Neoplasm Metastasis; Obesity; Operative Surgical Procedures; Outcome; PTEN gene; Paraffin Embedding; Pathology; Pathway interactions; Patients; Performance; Pharmaceutical Preparations; Phase; Phase II Clinical Trials; Prevention; Prevention approach; Process; Proteins; Proto-Oncogene Proteins c-akt; Recurrence; Research; Research Personnel; Resistance; Risk; Role; Safety; Scientist; Signal Pathway; Specialized Program of Research Excellence; Staging; Surgeon; Techniques; Testing; Therapeutic; Tissues; Translational Research; Treatment Efficacy; Tumor Antigens; United States; Uterine Cancer; Woman; advanced disease; angiogenesis; anti-cancer therapeutic; base; cancer cell; clinical decision-making; clinical practice; cohort; diabetic; diet and exercise; experience; high risk; human FRAP1 protein; improved; inhibitor/antagonist; innovation; mTOR Inhibitor; mortality; new therapeutic target; novel; novel strategies; novel therapeutics; overexpression; pre-clinical; prevent; programs; response; tumor; tumorigenesis

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).

MD 安德森癌症中心妇科癌症专业卓越研究计划 (SPORE) 的总体目标是开展高度创新的转化研究，以预防和治疗子宫癌。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制定新的治疗策略，2）在高危人群（包括肥胖女性）中推广化学预防子宫内膜癌的新策略，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 SPORE，我们建立了一个高产的子宫癌转化研究社区，其广度和深度都是无与伦比的。该提案包括 4 个由经验丰富的转化科学家领导的具有较高转化影响力和杰出科学价值的项目。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对肥胖、胰岛素抵抗女性进行化学预防的试验。项目 2“使用子宫内膜生物标志物预测晚期疾病”旨在确定 SPORE 头五年中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特定且重要的临床困境。项目 3“子宫癌中的 EphA2 靶向”重点关注新型治疗靶点 EphA2。 EphA2 在相当大比例的子宫癌中过度表达，与较差的总体生存率相关，并且已被证明可以调节血管生成。该项目将包括免疫偶联物的 Ib 期临床试验，该免疫偶联物将抗癌治疗剂与 EphA2 抗体连接起来。项目 4“靶向子宫内膜癌中的 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肿瘤发生中的作用。初步数据表明，该通路的多个节点中存在突变，并且对通路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。四核将支持这些项目。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）。