SPORE in Pancreatic Cancer

胰腺癌中的孢子

• 批准号: 6668172
• 负责人: JAMES L. ABBRUZZESE
• 金额: $ 90万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6668172
• 关键词: clinical research; molecular oncology; pancreas neoplasms

DESCRIPTION (provided by applicant): The University of Texas M. D. Anderson SPORE in Pancreatic Cancer is focused on translating recent observations in molecular biology, cellular signaling, and DNA repair to patient care. This application outlines a strong institutional effort to foster research on the etiology, biology, and treatment of human pancreatic cancer that will translate basic research findings into concrete clinical research protocols involving pancreatic cancer patients. To accomplish this goal, five projects are proposed: Project 1 - A Novel Therapeutic Gene, p202, and its Potential in Pancreatic Cancer Therapy seeks to credential a specific new protein target that is applicable to pancreatic cancer because of its ability to inhibit the activity of NF-KappaB. The successful development of this strategy will lead to direct therapeutic application using a gene transfer approach. Project 2 - Role of COX-2 in Pancreatic Cancer Progression and Therapy will explore the mechanism of Cox-2 overexpression in pancreatic cancer. This project will specifically examine the hypothesis that EGF-EGF receptor interactions control PLA2 and COX2 expression in pancreatic cancer cells and that COX-2 regulates an important cell survival pathway. To address this issue in patients, a clinical trial entitled "Assessment of Biological Markers of Response to Treatment with Celecoxib and OSl 774 in Patients with Advanced Pancreatic Cancer" is proposed. Project 3 - NFkB Signaling Pathways in Pancreatic Cancer Biology & Therapy explores the biochemical effects and biologic consequences of a series of strategies to inhibit the EGFR - Akt - NFKappaB signaling pathway. Each approach tested has potential clinical relevance to pancreatic cancer. To clinically assess the impact of EGFR inhibition, a clinical trial entitled "Phase II Randomized Trial of Anti-Epidermal Growth Factor Receptor (EGFR) Antibody Cetuximab vs. Cetuximab Plus Gemcitabine in Patients with Advanced Pancreatic Cancer" is proposed. Project 4 - Regulation of Pancreatic Cancer Angiogenesis and Metastasis by Transcription Factor Sp1 will examine the hypothesis that disregulated expression and activation of Sp1 is responsible for aberrant expression of multiple angiogenic molecules that generates the angiogenic phenotype and sustains tumor growth and metastasis. Project 5 - DNA Repair as a Risk Factor for Pancreatic Cancer tests the hypothesis that DNA repair capacity is a risk factor for pancreatic cancer, and that polymorphisms in DNA repair and cell cycle genes modulate the efficiency of DNA repair capacity thereby increasing individual risk of pancreatic cancer or response to therapy. Data from two clinical trials in patients with resectable pancreatic cancer will examine the effect of DNA repair on patient survival following multi-modality therapy. To support these efforts, two Cores are proposed: Core - Biostatistics and Information Management will provide biostatistical support for the design and analysis of all Projects and clinical trials conducted through the SPORE. Core - Tissue Procurement and Distribution will facilitate the acquisition and distribution of pancreatic cancer and normal tissue to all SPORE Projects and collaborators. This Core will also evaluate and distribute all tumor biopsies and blood obtained from the clinical trials. We believe that our well-developed program will provide a significant and sustained impact on pancreatic cancer translational research and identify new research opportunities that will have an impact in reducing pancreatic cancer incidence and mortality.

描述（由申请人提供）：德克萨斯大学 M. D. Anderson SPORE 胰腺癌研究重点是将分子生物学、细胞信号传导和 DNA 修复方面的最新观察结果转化为患者护理。该申请概述了机构为促进人类胰腺癌的病因学、生物学和治疗研究所做的强有力的努力，这些研究将把基础研究成果转化为涉及胰腺癌患者的具体临床研究方案。为了实现这一目标，提出了五个项目： 项目 1 - 新型治疗基因 p202 及其在胰腺癌治疗中的潜力旨在证明一种适用于胰腺癌的特定新蛋白质靶点，因为它能够抑制 NF-KappaB 的活性。该策略的成功开发将导致使用基因转移方法的直接治疗应用。项目2——COX-2在胰腺癌进展和治疗中的作用将探讨Cox-2在胰腺癌中过度表达的机制。该项目将具体研究以下假设：EGF-EGF 受体相互作用控制胰腺癌细胞中的 PLA2 和 COX2 表达，以及 COX-2 调节重要的细胞生存途径。为了解决患者的这个问题，提出了一项题为“评估晚期胰腺癌患者对塞来考昔和OS1 774治疗的反应的生物标志物”的临床试验。项目 3 - 胰腺癌生物学和治疗中的 NFkB 信号通路探讨了一系列抑制 EGFR - Akt - NFKappaB 信号通路策略的生化效应和生物学后果。每种测试方法都与胰腺癌具有潜在的临床相关性。为了临床评估EGFR抑制的影响，提出了一项题为“抗表皮生长因子受体（EGFR）抗体西妥昔单抗与西妥昔单抗加吉西他滨在晚期胰腺癌患者中的II期随机试验”的临床试验。项目 4 - 转录因子 Sp1 对胰腺癌血管生成和转移的调节将检验这样的假设：Sp1 的表达和激活失调导致多种血管生成分子的异常表达，从而产生血管生成表型并维持肿瘤生长和转移。项目 5 - DNA 修复作为胰腺癌的危险因素测试以下假设：DNA 修复能力是胰腺癌的危险因素，DNA 修复和细胞周期基因的多态性调节 DNA 修复能力的效率，从而增加个体患胰腺癌的风险或对治疗的反应。两项针对可切除胰腺癌患者的临床试验数据将检验多模式治疗后 DNA 修复对患者生存的影响。为了支持这些努力，提出了两个核心： 核心 - 生物统计学和信息管理将为所有项目的设计和分析以及通过 SPORE 进行的临床试验提供生物统计支持。核心 - 组织采购和分发将促进胰腺癌和正常组织的获取和分发给所有 SPORE 项目和合作者。该核心还将评估和分发从临床试验中获得的所有肿瘤活检和血液。我们相信，我们完善的计划将对胰腺癌转化研究产生重大和持续的影响，并确定新的研究机会，从而降低胰腺癌的发病率和死亡率。