Mayo Clinic SPORE in Ovarian Cancer

在女性癌症(乳腺癌和妇科癌症)中，卵巢癌的死亡率最高。梅奥诊所的卵巢癌孢子以基础、临床和人口科学研究人员为特色，进行旨在减轻卵巢癌负担的转化研究。这个孢子的翻译科学包括四个项目。项目1“PARP和拓扑异构酶I中毒治疗卵巢癌”，研究了聚腺苷二磷酸核糖聚合酶(PARP)抑制剂ABT-888单独和与拓扑替康联合使用的效果。除了阐明ABT-888如何将PARP转化为一种积极促进拓扑替康治疗的卵巢癌细胞死亡的酶外，该项目还将在Topotecan/ABT-888 II期试验中检查一系列肿瘤标记物预测反应的能力。项目2，“卵巢癌免疫抑制的机制”，我们的人口科学项目，研究卵巢癌微环境免疫抑制的成分。基于大量卵巢癌病例，这项工作将检查调节性T细胞相关基因的遗传变异、微环境中Tregs的数量以及诊断后结果的差异。项目3.“优化麻疹病毒疗法治疗复发性卵巢癌”建立在我们的体外和I期临床试验数据的基础上，这些数据表明，在复发卵巢癌妇女体内注射麻疹病毒减毒疫苗株具有良好的抗肿瘤活性。在这个项目中，我们将研究全身给药病毒的可能性，以及增强病毒细胞毒性的措施。项目4.梅奥公司的研究表明，黄烷醇与顺铂结合可产生细胞毒性协同作用，这项研究的基础是“黄烷醇逆转卵巢癌对铂的耐药性”。我们完成了这种组合的I期试验，现在在对铂类耐药卵巢癌的II期试验中，观察到33%的应答率，这是在这种情况下通常看到的平均应答率的两倍。该项目将研究协同作用的机制，并试图通过添加第三种药物和/或从有效与无效的肿瘤样本中识别预测生物标记物来改进组合。四个核心(管理、生物标本/患者登记、动物模型和生物统计学)为孢子的翻译研究提供基础设施支持。已经建立了一个发展研究计划，以促进有前途的研究计划；职业发展计划将促进希望从事卵巢癌转译研究的初级或更成熟的研究人员的研究生涯。梅奥诊所卵巢癌孢子得到了梅奥诊所癌症中心和梅奥基金会的全力支持。

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.