SPORE in Pancreatic Cancer

描述（由申请人提供）：这个胰腺腺癌（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，重点是转化研究。它的主题是基因治疗，死亡受体靶向免疫治疗，化疗耐药的生长因子机制，肿瘤基因抑制和蛋白质降解机制都是一个关键的优先事项。四个研究项目涉及跨学科的调查团队，包括：1.)“细胞毒性耐药：FGFR-1信号传导和逆转”将探讨FGFR-1差异信号转导的机制及其在临床胰腺癌细胞毒性（放化疗）耐药中的细胞毒性胰岛素（CR）耐药。2)。“肿瘤抑制因子DPC4/Smad4对胰腺癌蛋白不稳定性的机制”，该研究将评估Jab-1抑制和Smad4/DPC4蛋白降解作为胰腺肿瘤生长的潜在抑制剂的作用。3)。“胰腺癌的多模式靶向治疗-单独使用死亡受体（DR）抗体和联合化疗-放射相互作用”，这将为靶向免疫疗法提供早期翻译，通过抗DR5死亡受体抗体TR-8 （anti -DR5）治疗胰腺癌。4)。“用于胰腺癌的协调病毒-辅助疗法（CVAT）”，这将是一个基础性的开发和选择新的基因治疗载体，包括涉及RAID支持的条件复制RGD-COX-2腺病毒载体和FDA批准的HSV 207溶瘤性疱疹载体的早期翻译试验。这些项目将得到四个核心的支持：

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.