RELEVANCE OF GENOMIC ALTERATIONS IN COLORECTAL CANCER

基因组改变与结直肠癌的相关性

基本信息

  • 批准号:
    6194037
  • 负责人:
  • 金额:
    $ 109.09万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2000
  • 资助国家:
    美国
  • 起止时间:
    2000-09-30 至 2005-08-31
  • 项目状态:
    已结题

项目摘要

Carcinoma of the colon and rectum is currently the second leading cause of cancer-related mortality in the United States. Genetic susceptibility to this malignancy has been identified among individuals and families with familial adenomatous polyposis (FAP) and with hereditary non-polyposis colorectal cancer (HNPCC). However, the majority of colorectal cancer cases appear sporadic. There have been significant advances in understanding the genetic alterations associated with tumor progression pathways among individuals where the FAP gene (adenomatous polyposis coli; APC) is the first or an early event (the Aneuploid Pathway) as well as among HNPCC-affected individuals (the Mismatch Repair or MMR-Pathway). Central to the theme of this project is the hypothesis that the genetic alterations implicated in the Aneuploid- and MMR-Pathways of tumor progression are relevant to the diagnostic and therapeutic approaches of patients with sporadic colorectal cancers. This Program consists of three Projects of three Projects and three Core facilities. Project 1 has nine phase I/II clinical trials which will test multi- agent chemotherapy regimens including oral agents with our without pelvic radiation for patients with rectal cancer or metastatic colorectal cancer, respectively. Another goal of Project is to identify patients whose therapy an be rationally influenced by determination of genetic alterations associated with the Aneuploid-Pathway (Project 2) or MMR-pathway (Project 3) or tumor progression. It is expected that at least 230 tumors form clinical trip enrollees will be tested for MMR Status as well as the degree of expression of genes related to the Aneuploid Pathway. Investigators in Project 2 will use the APC system to further identify and characterize genes that influence the development of colorectal polyps/tumors. Additional studies of the Mom1 locus and a newly discovered tumor modifier named Mom2 will provide further insight into the Aneuploid-Pathway of colorectal tumor progression with the goal of prevention and therapeutic intervention. Project 3 researchers will continue to elucidate the structural and functional processes associated with mismatch repair genes now implicated in the development and progression of many hereditary and sporadic colorectal cancers. This work will enhance our understanding of the complex events in the MMR-pathway and also provide new diagnostic and prognostic methodologies to test in colorectal tumors.
结肠癌和直肠癌目前是美国癌症相关死亡率的第二大原因。在家族性腺瘤性息肉病(FAP)和遗传性非息肉病性结直肠癌(HNPCC)的个体和家族中,已经确定了对这种恶性肿瘤的遗传易感性。然而,大多数结直肠癌病例呈散发性。在理解与FAP基因(腺瘤性结肠息肉病; APC)是第一个或早期事件(非整倍体途径)的个体以及受HNPC影响的个体(错配修复或MMR途径)中肿瘤进展途径相关的遗传改变方面取得了重大进展。该项目的核心主题是假设肿瘤进展的非整倍体和MMR途径中涉及的遗传改变与散发性结直肠癌患者的诊断和治疗方法相关。该项目由三个项目和三个核心设施组成。项目1有9项I/II期临床试验,将分别测试直肠癌或转移性结直肠癌患者的多药化疗方案,包括口服药物和盆腔放疗。该项目的另一个目标是确定其治疗可以通过确定与非整倍体途径(项目2)或MMR途径(项目3)或肿瘤进展相关的遗传改变而合理影响的患者。预计将对来自临床旅行入组者的至少230个肿瘤进行MMR状态以及与非整倍体途径相关的基因表达程度的检测。项目2的研究人员将使用APC系统进一步识别和表征影响结直肠息肉/肿瘤发展的基因。对Mom 1基因座和一种新发现的肿瘤修饰因子Mom 2的进一步研究将进一步深入了解结直肠肿瘤进展的非整倍体途径,以预防和治疗干预为目标。项目3的研究人员将继续阐明与错配修复基因相关的结构和功能过程,这些基因现在与许多遗传性和散发性结直肠癌的发展和进展有关。这项工作将增强我们对MMR通路中复杂事件的理解,并提供新的诊断和预后方法来测试结直肠肿瘤。

项目成果

期刊论文数量(0)
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WALTER J CURRAN其他文献

WALTER J CURRAN的其他文献

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{{ truncateString('WALTER J CURRAN', 18)}}的其他基金

INNOVATIVE APPROACHES TO PATIENTS WITH ADENOCARCINOMA
腺癌患者的创新方法
  • 批准号:
    6653309
  • 财政年份:
    2002
  • 资助金额:
    $ 109.09万
  • 项目类别:
INNOVATIVE APPROACHES TO PATIENTS WITH ADENOCARCINOMA
腺癌患者的创新方法
  • 批准号:
    6651268
  • 财政年份:
    2002
  • 资助金额:
    $ 109.09万
  • 项目类别:
INNOVATIVE APPROACHES TO PATIENTS WITH ADENOCARCINOMA
腺癌患者的创新方法
  • 批准号:
    6499799
  • 财政年份:
    2001
  • 资助金额:
    $ 109.09万
  • 项目类别:
RELEVANCE OF GENOMIC ALTERATIONS IN COLORECTAL CANCER
基因组改变与结直肠癌的相关性
  • 批准号:
    6649584
  • 财政年份:
    2000
  • 资助金额:
    $ 109.09万
  • 项目类别:
RELEVANCE OF GENOMIC ALTERATIONS IN COLORECTAL CANCER
基因组改变与结直肠癌的相关性
  • 批准号:
    6522375
  • 财政年份:
    2000
  • 资助金额:
    $ 109.09万
  • 项目类别:
RELEVANCE OF GENOMIC ALTERATIONS IN COLORECTAL CANCER
基因组改变与结直肠癌的相关性
  • 批准号:
    6651156
  • 财政年份:
    2000
  • 资助金额:
    $ 109.09万
  • 项目类别:
RELEVANCE OF GENOMIC ALTERATIONS IN COLORECTAL CANCER
基因组改变与结直肠癌的相关性
  • 批准号:
    6493131
  • 财政年份:
    2000
  • 资助金额:
    $ 109.09万
  • 项目类别:
RELEVANCE OF GENOMIC ALTERATIONS IN COLORECTAL CANCER
基因组改变与结直肠癌的相关性
  • 批准号:
    6376305
  • 财政年份:
    2000
  • 资助金额:
    $ 109.09万
  • 项目类别:
RELEVANCE OF GENOMIC ALTERATIONS IN COLORECTAL CANCER
基因组改变与结直肠癌的相关性
  • 批准号:
    6777645
  • 财政年份:
    2000
  • 资助金额:
    $ 109.09万
  • 项目类别:
BREAST CANCER RESEARCH PROGRAM INTERGRATION/FORMALIZATIO
乳腺癌研究计划整合/正规化
  • 批准号:
    2109518
  • 财政年份:
    1994
  • 资助金额:
    $ 109.09万
  • 项目类别:
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