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：
10228046
负责人：
ALAN D. D'ANDREA
金额：
$ 226.41万
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/10228046
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.

项目概要（总体）此卵巢癌 SPORE 应用程序的总体部分描述了背景，三个项目和四个核心的具体目标、创新和研究计划。我们强调内部 SPORE 与伴随生物标志物的临床试验合作和开发。通过这个孢子应用程序中，我们试图解决卵巢癌治疗中几个最紧迫的问题。第一的， PARP 抑制剂是高级别浆液性卵巢癌 (HGSC) 治疗的一个新的基本特征，但是许多患者在服用这些药物后最终出现癌症进展。因此，在项目 1 中，我们有设计了药物组合的临床试验和相关研究，这将使我们能够系统地延长 PARP 抑制剂的使用。其次，我们认识到免疫疗法对实体瘤的新影响肿瘤治疗。因此，在项目 2 中，我们为卵巢癌患者设计了一种新型疫苗试验。第三， HGSC 患有原发性难治性疾病或癌症复发的患者潜在的 RAS 突变，例如低度浆液性或粘液性癌症，给临床带来了特别困难问题。因此，在项目3中，我们将探索新型非铂类药物组合，例如 BCL 抑制剂和 MEK 抑制剂的组合，并将检查预测生物标志物和肿瘤细胞外活动中明显的反应。该 DF/HCC 卵巢癌 SPORE 的具体目标如下目标 1（项目 1）：ATR 抑制剂介导的高级别浆液性 PARP 抑制剂耐药性逆转卵巢癌（HGSOC）；目标 2（项目 2）：将个人新抗原靶向癌症疫苗与卵巢癌的免疫检查点阻断；目标 3（项目 3）：评估 Trametinib 的疗效 + 纳维托克治疗复发性卵巢癌。