HCC Ovarian Cancer SPORE

项目摘要/摘要--总体 卵巢癌(Ovca)的死亡率和发病率位居第三，是第五大致癌原因。 美国女性的死亡。卵巢萎缩症患者的典型病程为四年半 确诊至死亡的时间。在护理病人的过程中，后天和先天的抵抗力 有效和有前景的治疗方法，如化疗、PARP抑制剂治疗和免疫治疗，推动 疾病的发展。UPMC Hillman癌症中心(肝细胞癌)卵子的总体目标是防止 和/或克服治疗阻力以提高患者存活率。孢子的三个项目中的每个 由孢子调查人员的创新概念和发现演变而来。每个项目都涉及一项临床试验。 和一个新经纪人在一起。此外，每个项目通过互补的调查员专业知识，将关键的 Translational的目标是确定最有可能对治疗有反应的患者。项目1将评估 表观遗传调节因子EZH2的抑制剂预防/克服OvCa基质祖细胞驱动的耐药 以铂为基础的化疗。项目2将确定下调BET抑制剂的关键 DNA修复和细胞周期检查点蛋白，可以逆转对PARP抑制剂的耐药性。项目3将测试 驱动肿瘤免疫排斥的Hedgehog信号通路的抑制剂是否能改善 卵巢癌患者对免疫检查点抑制剂治疗的反应。肝细胞癌Ovca孢子将包括职业生涯 增强计划(CEP)和发展研究计划(DRP)，以鼓励及早 职业调查员进入翻译OvCa研究领域，并聘请更多成熟的 卵泡刺激素研究的研究人员。CEP和DRP，这两个项目分担成本，并积极提供 向代表不足的少数群体的调查人员提供研究资金，将提供一条潜在的管道 未来的孢子项目。所有的孢子、CEP和DRP项目都将接受来自 管理核心和来自两个共享资源核心的支持。翻译病理学的核心意志 收集、注释、归档和分发来自300多个肝癌的生物标本和临床数据 每年都会有卵巢癌患者就诊。它还将开发新的临床前实验模型，其行为更像 人类卵泡刺激素。生物统计和生物信息学核心将协助设计和分析所有研究，包括 能够提供肿瘤内单个细胞的分子和空间特征的“组学”技术。 孢子项目还将得到现有的和新的合作者的支持，这些合作者是内部和 肝细胞癌的外部。结合起来，孢子项目、CEP、DRP和核心与我们的 垂直合作者，以改善卵巢癌患者的预后。调查结果是由 孢子将通过进一步的合作和未来的非孢子资助来推进。

PROJECT SUMMARY/ABSTRACT – OVERALL Ovarian cancer (OvCa) has the third highest mortality to incidence ratio and is the fifth leading cause of cancer death in American women. The typical disease course of a patient with OvCa spans four and a half years from the time of diagnosis to death. During the course of patient care, acquired and innate resistance to our most effective and promising therapies, such as chemotherapy, PARP inhibitor therapy, and immunotherapy, drives disease progression. The overall goal of the UPMC Hillman Cancer Center (HCC) OvCa SPORE is to prevent and/or overcome therapeutic resistance to improve patient survival. Each of the SPORE’s three Projects evolved from the innovative concepts and findings of SPORE investigators. Each project involves a clinical trial with a new agent. In addition, each project, through complementary investigator expertise, incorporates critical translational aims to identify patients most likely to respond to therapy. Project 1 will assess the ability of inhibitors of the epigenetic regulator EZH2 to prevent/overcome OvCa stromal progenitor cell-driven resistance to platinum-based chemotherapy. Project 2 will determine whether BET inhibitors, which downregulate critical DNA repair and cell cycle checkpoint proteins, can reverse resistance to PARP inhibitors. Project 3 will test whether inhibitors of the hedgehog signaling pathway, which drives tumor immune exclusion, can improve OvCa patient response to immune checkpoint inhibitor therapy. The HCC OvCa SPORE will include a Career Enhancement Program (CEP) and Developmental Research Program (DRP) in order to both encourage early career investigators to enter the field of translational OvCa research and engage more established investigators in OvCa research. The CEP and the DRP, which are cost-shared and proactive at providing research funding to investigators from under-represented minority groups, will provide a pipeline of potential future SPORE Projects. All SPORE, CEP, and DRP Projects will be receive fiscal and scientific oversight from an Administrative Core and support from two shared resource cores. The Translational Pathology Core will collect, annotate, archive, and distribute biospecimens and clinical data derived from the more than 300 HCC OvCa patients seen each year. It will also develop new preclinical experimental models that behave more like human OvCa. The Biostatistics and Bioinformatics Core will aid in design and analysis of all studies, including ‘omic’ technologies that can provide molecular and spatial characterization of individual cells within a tumor. The SPORE Projects will also be supported by established and new collaborators who are internal and external to HCC. Combined, the SPORE projects, CEP, DRP, and cores are positioned, together with our vertical collaborators, to improve the outcomes of patients with ovarian cancer. The findings generated by the SPORE will be advanced through further collaboration and future non-SPORE funding.