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Dana Farber/Harvard Cancer Center Ovarian Cancer SPORE grant

达纳法伯/哈佛大学癌症中心卵巢癌孢子补助金

基本信息

批准号：
10469368
负责人：
Cesar M Castro
金额：
$ 215.6万
依托单位：
DANA-FARBER CANCER INST
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-08-03 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10469368
关键词：
Address Advocate Area BCL1 Oncogene Basic Science Biological Biological Markers Biological Models Biometry Cancer Center Cancer Patient Cancer Vaccines Clinical Clinical Trials Clinical Trials Design Collaborations Combination immunotherapy Companions Correlative Study DNA Repair Dana-Farber Cancer Institute Decision Making Development Drug Combinations Funding General Hospitals Generations Grant Gynecologic Oncology Hospitals Human Immunotherapy In Vitro Institutes International Investigation Israel Laboratories Leadership MEKs Malignant Female Reproductive System Neoplasm Malignant Neoplasms Malignant neoplasm of ovary Massachusetts Mediating Mucinous Mutation Newly Diagnosed Occupational activity of managing finances Organoids Ovarian Carcinoma Pathology Patient-Focused Outcomes Patients Principal Investigator Recurrence Refractory Disease Relapse Research Research Personnel Resistance Role Scientist Serous Solid Neoplasm Specialized Program of Research Excellence Structure Technology Therapeutic Woman Writing anticancer research cancer therapy career clinical development design drug development drug sensitivity efficacy evaluation experience extracellular immune checkpoint blockade improved outcome inhibitor innovation medical schools member neoantigens novel novel drug combination novel vaccines oncology program predictive marker programs resistance mechanism response senior faculty translational progress tumor tumor progression vaccine trial

项目摘要

Project Summary (Overall) The Overall section of this Ovarian Cancer SPORE application describes the Background, Specific Aims, Innovation, and Research Plan of the three projects and four cores. We emphasize intra- SPORE collaborations and development of clinical trials with companion biomarkers. Through this SPORE application, we have tried to address several of the most urgent questions in ovarian cancer therapy. First, PARP inhibitors are a new and essential feature of high grade serous ovarian cancer (HGSC) therapy, but many patients eventually have cancer progression on these agents. Accordingly, in Project 1, we have designed clinical trials with drug combinations and correlative studies which will allow us to systematically extend the use of PARP inhibitors. Second, we recognize the emerging impact of immunotherapy on solid tumor treatment. Thus, in Project 2, we have designed a novel vaccine trial for ovarian cancer patients. Third, HGSC patients with primary refractory disease or those patients with recurrence whose cancer harbor underlying RAS mutations such as low grade serous or mucinous cancers pose a particularly difficult clinical problem. Accordingly, in Project 3, we will explore novel non-platinum drug combinations, such as the combination of a BCL inhibitor and a MEK inhibitor, and will examine predictive biomarkers and tumor responses evident in the extracellular activity. The Specific Aims of this DF/HCC ovarian cancer SPORE are as follows: Aim 1 (Project 1): ATR inhibitor-mediated reversal of PARP inhibitor resistance in high-grade serous ovarian cancer (HGSOC); Aim 2 (Project 2): Combined personal neoantigen-targeting cancer vaccines with immune checkpoint blockade for ovarian cancer; Aim 3 (Project 3): Evaluation of the Efficacy of Trametinib + Navitoclax in recurrent ovarian carcinoma.

项目总结（整体）