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：
10024413
负责人：
ALAN D. D'ANDREA
金额：
$ 248.31万
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/10024413
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/antagonist innovation medical schools member neoantigens novel novel drug combination novel vaccines oncology program predictive marker programs resistance mechanism response senior faculty 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.

项目摘要（总体）该卵巢癌孢子应用的整体部分描述了背景三个项目和四个核心的具体目的，创新和研究计划。我们强调内部孢子合作和与伴侣生物标志物的临床试验的开发。通过这个孢子应用，我们试图解决卵巢癌疗法中最紧迫的一些问题。第一的， PARP抑制剂是高级浆液卵巢癌（HGSC）疗法的新的重要特征，但是许多患者最终对这些药物的癌症进展。因此，在项目1中，我们有设计了使用药物组合和相关研究的临床试验，这将使我们能够系统地进行扩展使用PARP抑制剂。第二，我们认识到免疫疗法对固体的新兴影响肿瘤治疗。因此，在项目2中，我们为卵巢癌患者设计了一项新型疫苗试验。第三， HGSC原发性难治性疾病的患者或癌症携带的复发患者低级浆液或粘液癌等基本的RAS突变构成了特别困难的临床问题。因此，在项目3中，我们将探索新型的非铂药组合，例如 BCL抑制剂和MEK抑制剂的组合，将检查预测性生物标志物和肿瘤在细胞外活性中明显的反应。该DF/HCC卵巢癌孢子的具体目的是以下内容：AIM 1（项目1）：ATR抑制剂介导的PARP抑制剂耐药性的逆转卵巢癌（HGSOC）； AIM 2（项目2）：与个人新抗原的癌症疫苗结合在一起卵巢癌的免疫检查点封锁； AIM 3（项目3）：曲妥尼 +的功效评估复发性卵巢癌中的Navitoclax。