Targets to Therapeutics in Pancreatic Cancer

胰腺癌的治疗目标

• 批准号: 7271112
• 负责人: DANIEL D VON HOFF
• 金额: $ 312.97万
• 依托单位: TRANSLATIONAL GENOMICS RESEARCH INST
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7271112
• 关键词: Targets; Therapeutics; Pancreatic; Cancer

DESCRIPTION (provided by applicant): Pancreatic cancer is now the fourth leading cause of death from cancer in women and men in the United States. New, innovative approaches to the prevention and treatment of pancreatic cancer are sorely needed. This Program Project Grant (P01) application in pancreatic cancer takes up that challenging need, building on a strong foundation of interest and expertise in pancreatic cancer and in drug development at the Arizona Cancer Center (AZCC) at the University of Arizona. The central theme and goal of this P01 is to speed delivery into the clinic of new therapeutic agents against new targets in pancreatic cancer. The goal of this P01 is that in each year of this P01, we will deliver a new agent into clinical trials in patients with pancreatic cancer, which hits a target discovered and validated in one of the projects of this P01. This P01 application represents a revised application that we feel is an improved, more focused effort against the disease. Responses to each of the critiques are presented in the beginning of each section of the application. Two years ago, the AZCC formed the Sydney Salmon Pancreatic Cancer Team (named after the founding director of the AZCC who passed away from the disease). The team has built an infrastructure of investigators (established and new, in basic, translational, and clinical research), developed a patient base, begun a series of clinical trials, and created an ongoing forum for communicating new research initiatives and findings. In addition, Dr. .Von Hoff, the principal investigator for this application, has stepped down from the Directorship of the Arizona Cancer Center to devote full time to this effort. Our approach to make a difference against pancreatic cancer focuses on the development of innovative, translational ways to tackle the disease. Out of that groundwork effort comes this P01 application focusing on pancreatic cancer. As we hope the reviewers will see, our team has already made substantial progress in identifying new targets in and indeed new approaches to pancreatic cancer. This P01 application focuses that ongoing work and translates that work into new therapeutics that will be brought into patients. This P01 contains three translational research projects whose collective aims are to develop new therapeutics for patients with pancreatic cancer. These related Projects include: (1) Treatment of Hypoxia Resistance in Pancreatic Cancer; (2) Method to Eliminate Pancreatic Cells with Specific Patterns of Mutations/Deletions; and (3) Validation of Amplified Genes in Pancreatic Cancer: New sensitizing Targets for Improved Gemcitabine Therapy. Each project already has some leads and each project is designed to maximize translational potential. As will be seen in the application, the Projects are highly integrated so there is the highest probability we can bring that one therapeutic to the clinic each year. The projects are supported by four highly-integrated shared services (cores): (1) Pancreatic Cancer Biospecimens Repository; (2) Pattern Analysis and Computational Biology Core; (3) Drug Development Core; and (4) Evaluation and Administration Core. These cores provide material, informatic, development and administrative support for the projects. Since we are blessed by having such excellent shared services at the Arizona Cancer Center (AZCC), the cores in this proposed P01 are designed to utilize those cores and therefore for this application we are only asking for resources to provide the services that are over an above the services that can be provided by these AZCC cores. In addition, both internal and external scientific advisory boards are included in the P01 to assure maximum input into the science and into the execution of the Projects. The overall goal of this P01 is the delivery into the clinic one new therapeutic agent against a new target in pancreatic cancer each year of the P01. We feel this effort, with new approaches to pancreatic cancer, concentrated in a P01, has a chance to make an impact on the disease.

描述（由申请人提供）：胰腺癌现在是美国男女癌症死亡的第四大死亡原因。迫切需要进行预防和治疗胰腺癌的新的创新方法。该计划项目赠款（P01）在胰腺癌中的申请提出了挑战性的需求，基于亚利桑那大学亚利桑那癌症中心（AZCC）的胰腺癌和药物开发的强大基础和专业知识的基础。该P01的核心主题和目标是加快针对胰腺癌新靶标的新治疗剂诊所的诊所。该P01的目的是，在本P01的每一年中，我们将在胰腺癌患者的临床试验中运送一个新代理，该试验击中了该P01项目之一中发现和验证的目标。 该P01应用代表了我们认为对疾病的改进，更集中的努力。对每个批评的响应都在应用程序的每个部分的开头中提出。 两年前，AZCC组成了悉尼鲑鱼胰腺癌团队（以从该疾病中去世的AZCC的创始董事命名）。该团队已经建立了研究人员的基础设施（基本，转化和临床研究成立和新的），开发了一个患者基础，开始了一系列临床试验，并创建了一个正在进行的论坛，用于传达新的研究计划和发现。此外，该应用程序的主要研究人员Von Hoff博士已从亚利桑那癌症中心的董事职位辞职，全职致力于这项工作。我们对胰腺癌有所作为的方法着重于创新的，转化的方法来解决该疾病。这项P01申请的重点是胰腺癌。正如我们希望审稿人能看到的那样，我们的团队已经在确定胰腺癌的新目标（甚至是新的方法）方面取得了重大进展。该P01应用程序集中于正在进行的工作，并将其转化为将带入患者的新治疗剂。 该p01包含三个转化研究项目，其集体目的是为胰腺癌患者开发新的治疗剂。这些相关项目包括：（1）治疗胰腺癌中缺氧性耐药性； （2）消除具有突变/缺失模式的胰腺细胞的方法； （3）胰腺癌中放大基因的验证：改善吉西他滨治疗的新敏感靶标。每个项目已经有一些潜在客户，每个项目旨在最大程度地发挥翻译潜力。从应用程序中可以看出，这些项目是高度集成的，因此我们每年可以将一种治疗性带到诊所。 这些项目得到了四个高度集成的共享服务（核心）的支持：（1）胰腺癌生物胶囊存储库； （2）模式分析和计算生物学核心； （3）药物发育核心； （4）评估和管理核心。这些核心为项目提供了物质，信息，开发和行政支持。 由于我们在亚利桑那州癌症中心（AZCC）拥有如此出色的共享服务而感到幸运，因此该拟议的P01中的核心旨在利用这些核心，因此，对于此应用程序，我们只要求资源提供这些AZCC核心可以提供的服务的服务。此外，内部和外部科学咨询委员会都包含在P01中，以确保对科学的最大投入和项目执行。 该P01的总体目标是每年针对P01的胰腺癌新靶标进入诊所一种新的治疗剂。我们感到这种努力以胰腺癌的新方法集中在P01中，有机会对疾病产生影响。