Mayo Clinic SPORE in Ovarian Cancer

梅奥诊所 SPORE 治疗卵巢癌

• 批准号: 7714977
• 负责人: LYNN C. HARTMANN
• 金额: $ 230万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7714977
• 关键词: Mayo; Clinic; SPORE; Ovarian; Cancer

DESCRIPTION (provided by applicant): Ovarian cancer has the highest mortality rate of the "women's cancers" (breast and gynecologic cancers). The Mayo Clinic SPORE in Ovarian Cancer features a team of basic, clinical, and population science Investigators conducting translational research designed to reduce the burden of ovarian cancer. The translational science of this SPORE includes four projects. Project 1, "Poisoning of PARP and topoisomerase I to treat ovarian cancer," studies the effect of the poly(ADP-ribose) polymerase (PARP) inhibitor ABT-888 alone and In combination with topotecan. In addition to elucidating how ABT-888 converts PARP Into an enzyme that actively contributes to the demise of topotecan-treated ovarian cancer cells, this project will examine a series of tumor markers for their ability to predict response in a topotecan/ABT-888 phase II trial. Project 2, "Mechanisms of immunosuppression in ovarian cancer," our population sciences project, studies the components of microenvironmental immunosuppression in ovarian cancer. Based in a large cohort of ovarian cancer cases, the work will examine differences in inherited variation in regulatory T-cell-related genes, the quantity of Tregs In the microenvironment and outcome after diagnosis. Project 3. "Optimizing measles virotherapy in the treatment of recurrent ovarian cancer," builds upon our in vitro and phase I clinical trial data showing promising anti-tumor activity with the attenuated vaccine strain of measles virus delivered intraperitoneally in women with recurrent ovarian cancer. In this project we will study the possibility of systemic administration of the virus and measures to enhance cytotoxicity of the virus. Project 4. "Flavopiridol reverses platinum resistance in ovarian cancer," builds upon work at Mayo showing that flavopiridol combines with cisplatin to yield cytotoxic synergy. We completed a phase I trial of this combination and now in a phase II trial in platinum-resistant ovarian cancer, have observed a 33% response rate, which is twice the mean response rate typically seen in this setting. This project will study the mechanism of synergy and attempt to improve upon the combination by adding a third agent and/or identifying predictive biomarkers in tumor samples from responders vs. non-responders. Four cores (Administration, Biospecimens/Patient Registry, Animal Models, and Biostatistics) provide the infrastructure support for the translational research of the SPORE. A Developmental Research Program has been established to foster promising research initiatives; and a Career Development Program will promote the research careers of junior or more established investigators who wish to pursue ovarian cancer translational research. The Mayo Clinic SPORE in Ovarian Cancer has the full support of the Mayo Clinic Cancer Center and Mayo Foundation.

描述（申请人提供）：卵巢癌是“女性癌症”（乳腺癌和妇科癌症）中死亡率最高的。梅奥诊所卵巢癌 SPORE 拥有一支由基础、临床和人口科学研究人员组成的团队，开展旨在减轻卵巢癌负担的转化研究。该 SPORE 的转化科学包括四个项目。项目 1“PARP 和拓扑异构酶 I 中毒治疗卵巢癌”研究聚（ADP-核糖）聚合酶（PARP）抑制剂 ABT-888 单独使用以及与拓扑替康联合使用的效果。除了阐明 ABT-888 如何将 PARP 转化为积极促进拓扑替康治疗的卵巢癌细胞死亡的酶外，该项目还将检查一系列肿瘤标记物预测拓扑替康/ABT-888 阶段反应的能力二审。项目 2“卵巢癌免疫抑制机制”是我们的人口科学项目，研究卵巢癌微环境免疫抑制的组成部分。这项工作以大量卵巢癌病例为基础，将检查调节性 T 细胞相关基因的遗传变异差异、微环境中 Tregs 的数量以及诊断后的结果。项目 3.“优化麻疹病毒疗法治疗复发性卵巢癌”以我们的体外和 I 期临床试验数据为基础，这些数据显示腹膜内注射的麻疹病毒减毒疫苗株对复发性卵巢癌女性具有良好的抗肿瘤活性。在这个项目中，我们将研究病毒全身给药的可能性以及增强病毒细胞毒性的措施。项目 4：“黄酮吡醇逆转卵巢癌中的铂耐药性”，以 Mayo 的研究为基础，该研究表明黄酮吡醇与顺铂结合可产生细胞毒性协同作用。我们完成了该组合的 I 期试验，现在正在进行铂耐药卵巢癌的 II 期试验，观察到 33% 的缓解率，这是这种情况下通常看到的平均缓解率的两倍。该项目将研究协同作用机制，并尝试通过添加第三种药物和/或识别应答者与非应答者肿瘤样本中的预测生物标志物来改进组合。四个核心（管理、生物样本/患者登记、动物模型和生物统计学）为 SPORE 的转化研究提供基础设施支持。制定了发展研究计划，以促进有前途的研究举措；职业发展计划将促进希望从事卵巢癌转化研究的初级或资深研究人员的研究生涯。梅奥诊所 SPORE 卵巢癌治疗项目得到了梅奥诊所癌症中心和梅奥基金会的全力支持。