SPORE in Pancreatic Cancer

胰腺癌中的孢子

• 批准号: 7121040
• 负责人: JAMES L. ABBRUZZESE
• 金额: $ 111.92万
• 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/7121040
• 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）：德克萨斯大学安德森癌症研究中心专注于将分子生物学、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。本申请概述了一项强有力的机构努力，以促进对人类胰腺癌的病因学、生物学和治疗的研究，将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 -一种新的治疗基因p202及其在胰腺癌治疗中的潜力，旨在证明一种特定的新蛋白靶点，由于其抑制NF-KappaB活性的能力而适用于胰腺癌。这一策略的成功发展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胰腺癌中COX-2过表达的机制。本项目将专门研究EGF-EGF受体相互作用控制胰腺癌细胞PLA2和COX2表达以及COX-2调节重要细胞存活途径的假设。为了解决患者的这一问题，提出了一项名为“晚期胰腺癌患者对塞来昔布和OSl 774治疗反应的生物标志物评估”的临床试验。项目3 -胰腺癌生物学与治疗中的NFkB信号通路探讨了抑制EGFR - Akt - NFKappaB信号通路的一系列策略的生化效应和生物学后果。所测试的每种方法都与胰腺癌有潜在的临床相关性。为了临床评估EGFR抑制的影响，提出了一项名为“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控将检验Sp1的表达和激活失调是导致多种血管生成分子异常表达的原因，这些分子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，测试了DNA修复能力是胰腺癌的危险因素的假设，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。来自可切除胰腺癌患者的两项临床试验的数据将检验DNA修复对多模式治疗后患者生存的影响。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通过孢子进行的所有项目和临床试验的设计和分析提供生物统计学支持。核心组织采购和分配将促进胰腺癌和正常组织的获取和分配给所有孢子项目和合作者。该中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，我们完善的项目将为胰腺癌转化研究提供重大和持续的影响，并确定新的研究机会，这将对降低胰腺癌发病率和死亡率产生影响。