UAB / UMN SPORE in Pancreatic Cancer

六年前，我们的UAB孢子在胰腺癌中的应用部分是由P-20基金资助的。资金有限；我们的迷你孢子由2个主要项目，3个核心和一个发展研究计划组成。在最初的资助期间，《孢子》科学的翻译导致了两个I期试验，一个II期试验和一个新的MRI成像试验。SPORE的研究人员发表了88篇与SPORE项目或胰腺癌相关的论文。发展研究基金产生了两个主要项目，项目1和项目4在这个续期申请中，2名获奖者成为项目的共同领导。三年前，Vickers博士（SPORE PI）成为明尼苏达大学（UMN）外科主席，我们重组为联合UAB/UMN胰腺癌SPORE。联合孢子运作良好，本提案是我们对孢子资金（PSO申请）的修订竞争性更新。本课题有4个主要项目：项目一是利用蛋白质组学技术在转基因动物模型中鉴定预测早期胰腺癌的生物标志物；项目2是一个延续项目，正在研究多种方法来提高抗dr5单克隆抗体在胰腺癌动物模型和患者中的治疗效果；项目3利用从人类胰腺癌（PCa）样本中获得的基因组和遗传数据以及从小鼠PCa模型中观察到的数据来了解驱动这种疾病转移和治疗耐药性的遗传事件。这些研究将导致I期临床试验；项目4是针对胰腺癌干细胞样肿瘤细胞治疗转移性胰腺癌的工程新型条件复制腺病毒载体。四个重要而有效的核心是：1)管理；2)组织资源与分子病理学；3)生物统计学;4)临床管理与试验（倡导子核心）。我们还要求支持我们的发展研究和职业发展项目，包括莫尔豪斯医学院和塔斯基吉大学。该申请得到了UAB和UMN强有力的机构支持，优秀的胰腺癌人群，并符合联邦指南。

Six years ago, our UAB SPORE in Pancreatic Cancer application was partially funded via a P-20 grant. With limited funding; our mini-SPORE was composed of 2 major projects, 3 Cores and a Developmental Research Program. During this initial funding period, translation of SPORE science resulted in two phase I trials, one Phase II trial and a novel MRI imaging trial. The investigators of the SPORE have 88 publications relating to SPORE projects or pancreatic cancer. The Developmental Research funding resulted in two major projects, Projects 1, & 4 in this renewal application and 2 awardees becoming Project co-leaders. Three years ago, Dr. Vickers (SPORE PI) became Chairman of Surgery at the University of Minnesota (UMN) and we restructured into a joint UAB/UMN SPORE in Pancreatic Cancer. The joint SPORE has functioned well and this proposal is our amended competitive renewal for full SPORE funding (PSO application). This proposal has 4 major projects: Project 1 is utilizing proteomic techniques in transgenic animal models to identify biomarkers that are predictive of early stage pancreatic cancer; Project 2 is a continuation project which is examining multiple methods to enhance the therapeutic efficacy of anti-DR5 monoclonal antibodies in pancreatic cancer animal models and patients; Project 3 is utilizing genomic and genetic data obtained from human pancreatic cancer (PCa) samples and observations from mouse models of PCa to understand the genetic events that drive metastasis and treatment resistance in this disease. These studies will lead to a phase I clinical trial; Project 4 is engineering novel conditionally replicative adenoviral vectors that target pancreatic cancer stem cell-like tumor cells for the treatment of metastatic pancreatic cancer. The four important and effective Cores are: 1) Administration; 2) Tissue Resource and Molecular Pathology; 3) Biostatistics; and 4) Clinical Management and Trials (Advocacy Sub-Core). We also request support for continuation of our Developmental Research and Career Development Programs which includes Morehouse School of Medicine and Tuskegee University. The application has strong institutional support from UAB and UMN, excellent pancreatic cancer populations and concurrence with federal guidelines.