SPORE in Pancreatic Cancer

描述(申请人提供)：这一胰腺癌(癌)孢子将极大地加强和扩大UAB综合癌症中心的胰腺癌研究，重点是转译研究。它的主题包括基因治疗、死亡受体靶向免疫治疗、生长因子耐药机制以及肿瘤基因抑制和蛋白质降解机制，这些都是关键优先事项。4个研究项目涉及跨学科调查小组，包括：1.)《细胞毒耐药：FGFR-1信号转导与逆转》，将探讨FGFR-1差异信号转导机制及其在临床胰腺癌细胞毒(放化疗)耐药中对细胞毒性胰岛素(CR)的抵抗。2.)《肿瘤抑制因子DPC4/Smad4对胰腺癌蛋白质不稳定的作用机制》，将评估JAB-1抑制和Smad4/DPC4蛋白降解作为潜在的胰腺肿瘤生长抑制因子的作用。3.)“胰腺癌的多模式靶向治疗-单独使用死亡受体(DR)抗体以及与化疗-放射相互作用相结合”，将为通过抗DR5死亡受体抗体TR-8(抗DR5)治疗胰腺癌的靶向免疫治疗提供早期翻译。4.)“协同病毒辅助治疗(CVAT)治疗胰腺癌”将是新的基因治疗载体的基础开发和选择，包括包括RAID支持的条件复制型RGD-COX-2腺病毒载体和FDA批准的HSV 207溶瘤疱疹病毒载体的早期翻译试验。这些项目将得到四个核心的支持： 1)行政/生物统计核心；2.)《组织资源与免疫病理学核心》；临床核心，和4.)动物模型和影像核心。此外，孢子还将有一个针对胰腺癌转化性研究职业的职业发展计划(5个奖项)和一个发展研究计划(每年4个试点项目)。该孢子有强大的机构承诺和热情的计划与其他孢子相互作用，包括我们自己的大脑，乳房和卵巢癌孢子。这种孢子将增加科学发现，并迅速将发现转化为创新的临床试验。

DESCRIPTION (provided by applicant): This Pancreatic Adenocarcinoma (Cancer) SPORE will greatly strengthen and expand the pancreatic cancer research of the UAB Comprehensive Cancer Center with an emphasis on translational research. Its themes of Gene Therapy, Death Receptor Targeted Immunotherapy, Growth Factor Mechanisms of chemoresistance, and mechanisms of Tumor Gene Suppression and Protein Degradation are all a critical priority. Four research projects involve interdisciplinary investigative teams including: 1.) "Cytotoxic Resistance: FGFR-1 Signaling and Reversion" which will explore the mechanism of FGFR-1 differential signal transduction and its resistance to cytotoxic insulin (CR) in cytotoxic (chemoradiation) resistance demonstrated in clinical pancreatic cancer. 2.) "Mechanisms of Tumor Suppressor DPC4/Smad4for Protein Instability in Pancreatic Cancer" which will evaluate the role of Jab-1 inhibition and Smad4/DPC4 protein degradation as potential inhibitor of pancreatic tumor growth. 3.) "Multimodality Targeted Therapy of Pancreatic Cancer - Use of Death Receptor (DR) Antibodies Alone and in Combination with Chemotherapy-Radiation Interactions" which will provide early translation for targeted immunotherapy to treat pancreatic cancer via anti DR5 death receptor antibody TR-8 (Anti-DR5). 4.) "Coordinated Virus - Adjunctive therapies (CVAT) for Pancreatic Cancer" which will be a fundamental development and selection of novel gene therapy vectors including early translation trial involving RAID supported conditionally replicative RGD-COX-2 adenoviral vector and a FDA approved HSV 207 oncolytic herpes vector. These projects will be supported by four Cores: 1.) Administrative/Biostatistics Core; 2.) Tissue Resource & Immunopathology Core; 3.) Clinical Core, and 4.) Animal Model and Imaging Core. In addition, the SPORE will have a Career Development Program directed at careers in Pancreatic Cancer Translational Research (5 awards) and a Developmental Research Program (4 pilot projects annually). The SPORE has strong institutional commitments and enthusiastic plans for interaction with other SPOREs including our own Brain, Breast, and Ovarian Cancer SPORE. This SPORE will increase scientific discoveries and rapidly translate findings into innovative clinical trials.