SPORE in Ovarian Cancer

卵巢癌孢子：综述 卵巢癌是美国女性中最具侵袭性的癌症之一，也是 癌症发病率和死亡率。约翰霍普金斯大学-宾夕法尼亚大学卵巢癌孢子 应用重点是通过转化新的实验室研究来降低卵巢癌的发病率和死亡率 我们机构在卵巢癌检测和治疗方面的改进发现。如此之高 翻译计划包含四个假设驱动的研究项目，三个核心资源，职业 增强计划和发展研究计划。项目1的目标是确定 检测宫颈液基标本中的肿瘤细胞、子宫内膜腔刷检和/或 血液中循环肿瘤DNA(CtDNA)可识别早期和低容量卵巢高级别浆膜腔积液 卵巢癌(HGSC)是最常见的卵巢癌类型，或其前驱病变浆液性输卵管 上皮内癌。项目2和项目3的目标是提供关键的临床前和早期临床 开发更有效的综合疗法治疗晚期卵巢HGSC，特别是复发的数据 疾病。具体地说，项目2是优化高级别卵巢浆液性卵巢癌的合成致死率 使用ATR抑制剂和PARP抑制剂。基于我们团队最近的一项发现的项目3提出 应用BET抑制剂克服铂耐药。项目4旨在确定抑制 脾酪氨酸激酶(SYK)活性使卵巢癌细胞对紫杉醇的细胞毒作用敏感 确定SYK抑制剂是否代表一种有希望与(每周)紫杉醇联合治疗的新药物 晚期卵巢癌的治疗。 这些项目由一个管理核心、一个生物库/病理核心和一个生物统计支持 核心。最后，职业提升和发展研究方案由人力资源管道组成 资本和创新想法，这将推动未来的孢子进步。此应用程序具有很强的 得到机构承诺的支持，以确保其成功。

OVARIAN CANCER SPORE: SUMMARY Ovarian cancer is one of the most aggressive cancers in women in the United States and a major cause of cancer morbidity and mortality. This Johns Hopkins-University of Pennsylvania Ovarian Cancer SPORE application focuses on reducing ovarian cancer incidence and mortality by translating new laboratory research discoveries made in our institution into improvements in ovarian cancer detection and treatment. This highly translational program contains four hypothesis-driven Research Projects, three Core Resources, the Career Enhancement Program, and the Developmental Research Program. The objective of Project 1 is to determine whether detection of tumor cells from liquid-based cervical fluid specimens, endometrial cavity brushing and/or circulating tumor DNA (ctDNA) from blood can identify early and low-volume ovarian high-grade serous carcinoma (HGSC), the most common type of ovarian carcinoma, or its precursor lesion, serous tubal intraepithelial carcinoma. The goal of Project 2 and Project 3 is to provide critical preclinical and early clinical data for developing more effective combined therapy to treat advanced ovarian HGSC, especially for recurrent diseases. Specifically, Project 2 is to optimize synthetic lethality in high-grade ovarian serous ovarian cancer by using ATR inhibitor and PARP inhibitor. Project 3 based on a recent discovery made by our team proposes to apply BET inhibitors for overcoming platinum resistance. Project 4 aims to determine that inhibition of Spleen Tyrosine Kinase (SYK) activity sensitizes ovarian cancer cells to the cytotoxic effect of paclitaxel, and determine if SYK inhibitor represents a promising new agent to be combined with (weekly) paclitaxel for the treatment of advanced ovarian cancer. These Projects are supported by an Administrative Core, a Biorepository/Pathology Core, and a Biostatistics Core. Finally, the Career Enhancement and Developmental Research Programs comprise pipelines of human capital and innovative ideas, respectively, which will fuel future SPORE advances. This application is strongly supported by institutional commitment to ensure its success.