SPORE in Ovarian Cancer

卵巢癌中的孢子

• 批准号: 10478838
• 负责人: IE-MING SHIH
• 金额: $ 158.91万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-18 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10478838
• 关键词: Address; Adjuvant Therapy; Affect; Biostatistics Core; Blood; Cancer Biology; Cancer Etiology; Cancer Patient; Carboplatin; Carcinoma; Carcinoma in Situ; Cervical; Cessation of life; Clinical; Clinical Data; Combined Modality Therapy; Complex; DNA Damage; Data; Detection; Developed Countries; Development; Diagnosis; Disease; Disease remission; Drug resistance; Early Diagnosis; Early treatment; Ensure; Five-Year Plans; Funding; Future; Genetic; Genomics; Goals; Histologic; Incidence; Institution; Laboratory Research; Lesion; Libraries; Liquid substance; Malignant Female Reproductive System Neoplasm; Malignant Neoplasms; Malignant neoplasm of ovary; Measurable; Medical; Molecular; Molecular Genetics; Monitor; Morbidity - disease rate; New Agents; Operative Surgical Procedures; Outcome; Ovarian; Ovarian Carcinoma; Paclitaxel; Pathologic; Pathology; Pathway interactions; Patient advocacy; Patients; Pennsylvania; Perioperative; Platinum; Prevention; Progress Review Group; Progression-Free Survivals; Proteomics; Recurrent disease; Reproduction spores; Research; Research Project Grants; Resistance; Resources; Risk Marker; SYK gene; Scientist; Screening for Ovarian Cancer; Serous; Specimen; Technology; Testing; TimeLine; Translating; Translational Research; Translations; Treatment outcome; Tube; Tumor Biology; Tyrosine Kinase Inhibitor; United States; Universities; Uterine cavity; Woman; Work; anticancer research; antitumor effect; base; biobank; biomarker identification; cancer cell; cancer therapy; career; chemotherapy; clinical application; collaborative environment; combat; cytotoxic; drug development; effective therapy; human capital; improved; inhibitor; innovation; mortality; multimodality; neoplastic cell; novel; novel strategies; novel therapeutic intervention; pre-clinical; programs; success; technology development; translational applications; tumor; tumor DNA; tumor heterogeneity

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.

卵巢癌孢子：总结 卵巢癌是美国女性中最具侵袭性的癌症之一，也是导致卵巢癌的主要原因。 癌症发病率和死亡率。这约翰霍普金斯大学宾夕法尼亚州卵巢癌孢子 应用的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 我们研究所的研究成果用于改善卵巢癌的检测和治疗。这种高度 翻译计划包含四个假设驱动的研究项目，三个核心资源，职业生涯 增强计划和发展研究计划。项目1的目标是确定 是否从液基宫颈液标本中检测肿瘤细胞，子宫内膜腔刷和/或 来自血液的循环肿瘤DNA（ctDNA）可以识别早期和低容量的卵巢高级别浆液性肿瘤。 卵巢癌（HGSC），最常见的卵巢癌类型，或其前体病变，浆液性输卵管癌， 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 开发更有效的联合治疗晚期卵巢HGSC的数据，特别是复发性 疾病具体而言，项目2是优化高级别卵巢浆液性卵巢癌的合成致死率 通过使用ATR抑制剂和PARP抑制剂。项目3基于我们团队最近的一项发现， 应用BET抑制剂以克服铂抗性。项目4的目的是确定抑制 脾酪氨酸激酶（SYK）活性使卵巢癌细胞对紫杉醇的细胞毒性作用敏感， 确定SYK抑制剂是否代表一种有前途的新药物，可与紫杉醇（每周一次）联合治疗 晚期卵巢癌的治疗 这些项目由一个行政核心、一个生物储存/病理学核心和一个生物统计学核心支持。 核心最后，职业提升和发展研究计划包括人力资源的管道， 资本和创新理念，这将推动未来的SPORE进步。该应用程序强烈 并得到机构承诺的支持，以确保其成功。

项目成果

Chimeric Antigen Receptors Expand the Repertoire of Antigenic Macromolecules for Cellular Immunity.

• DOI: 10.3390/cells10123356
• 发表时间: 2021-11-30
• 期刊: Cells
• 影响因子: 6
• 作者: Keane JT;Posey AD Jr
• 通讯作者: Posey AD Jr

Tumor Innervation: Cancer Has Some Nerve.

• DOI: 10.1016/j.trecan.2020.07.005
• 发表时间: 2020-12
• 期刊: Trends in cancer
• 影响因子: 18.4
• 作者: Reavis HD;Chen HI;Drapkin R
• 通讯作者: Drapkin R

Oncogenic BRAF and KRAS mutations in endosalpingiosis.

• DOI: 10.1002/path.5353
• 发表时间: 2020-02
• 期刊: The Journal of pathology
• 作者: Chui MH;Shih IM
• 通讯作者: Shih IM

Performance of computational algorithms to deconvolve heterogeneous bulk ovarian tumor tissue depends on experimental factors.

• DOI: 10.1186/s13059-023-03077-7
• 发表时间: 2023-10-20
• 期刊: GENOME BIOLOGY
• 影响因子: 12.3
• 作者: Hippen, Ariel A.;Omran, Dalia K.;Weber, Lukas M.;Jung, Euihye;Drapkin, Ronny;Doherty, Jennifer A.;Hicks, Stephanie C.;Greene, Casey S.
• 通讯作者: Greene, Casey S.

Unraveling the Mysteries of PAX8 in Reproductive Tract Cancers.

• DOI: 10.1158/0008-5472.can-20-3173
• 发表时间: 2021-02-15
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Chaves-Moreira D;Morin PJ;Drapkin R
• 通讯作者: Drapkin R