Identification of cancer stem cell therapeutic targets

说明3 总体计划3 项目和核心讨论摘要5 脊椎动物7 个别项目和核心8 项目1：确定癌症干细胞的自我更新途径并开发治疗性药理干预措施8 项目2：CD47对人白血病和其他肿瘤干细胞Cells........................................................................................................的靶向治疗15. 项目3：微流控技术用于基因表达、染色质结构的分子和功能分析，以及癌症干细胞的体外培养21 核心A：生物信息学核心27 核心B：流式细胞仪核心28 核心C：动物核心30 核心D：管理核心32 委员会预算建议35 特别强调小组名册 描述(由申请者提供)：这项响应RFA-CA-08-020的计划项目资助名为“肿瘤干细胞在癌症生物学、预防和治疗中的作用”。最近的证据表明，癌症有一个细胞层次，在这个层次上，被称为癌症干细胞的少数癌细胞群体驱动肿瘤的生长和扩散。前瞻性地识别致瘤癌细胞的能力将有助于识别调控其生长、转移和患者生存的途径。以自我更新等基本过程中涉及的途径为目标可能会导致更有效的治疗。这项提案是一系列相互关联的项目，旨在确定针对乳腺癌和白血病干细胞的新的癌症干细胞治疗靶点，并在临床前癌症干细胞模型中测试针对其中一些靶点的药物。我们计划的三个项目如下所示。项目1：乳腺癌干细胞自我更新途径的确定和治疗性药理学干预措施的发展。派·迈克·克拉克，斯坦福大学。项目2：CD47在人类白血病和其他癌症干细胞上的治疗靶点PI，Irv Weissman，斯坦福大学。项目3：微流控技术用于癌症干细胞的基因表达、染色质结构和体外培养的分子和功能分析。派·史蒂夫·奎克，斯坦福大学。这些项目高度相互联系，相互依赖，才能取得个别项目的成功以及本项目的成功。每个项目将得到4个核心的支持：一个行政核心、一个生物信息学核心、一个动物模型核心和一个流式细胞仪核心。

DESCRIPTION 3 OVERALL PROGRAM 3 PROJECT AND CORE SUMMARIES OF DISCUSSION 5 VERTEBRATE ANIMALS 7 INDIVIDUAL PROJECTS AND CORES 8 PROJECT 1: Identification of Self-renewal Pathways in Cancer Stem Cells and Development of Therapeutic Pharmacological Interventions 8 PROJECT 2: Therapeutic Targeting of CD47 on Human Leukemia and Other Cancer Stem Cells...............................................................................................................................15 PROJECT 3: Microfluidic techniques for the molecular and functional analysis of gene expression, chromatin structure, and for in vitro culturing of cancer stem cells 21 CORE A: Bioinformatics Core 27 CORE B: Flow Cytometry Core 28 CORE C: Animal Core 30 CORE D: Administrative Core 32 COMMITTEE BUDGET RECOMMENDATIONS 35 SPECIAL EMPHASIS PANEL ROSTER DESCRIPTION (provided by applicant): This program project grant in response to RFA-CA-08-020 is entitled "Tumor Stem Cells in Cancer Biology, Prevention, and Therapy." Recent evidence suggests that cancers have a cellular hierarchy in which a minority population of cancer cells, called cancer stem cells, drives the growth and spread of a tumor. The ability to prospectively identify tumorigenic cancer cells will facilitate the identification of pathways that regulate their growth, metastasis and survival in patients. Targeting the pathways involved in essential processes such as self renewal may lead to more effective therapies. This proposal is an interlocking set of projects designed to identify new cancer stem cell therapeutic targets against breast cancer and leukemia stem cells and to test drugs against some of these targets in a preclinical cancer stem cell model. The three projects of our Program are listed below. Project 1: Identification of self-renewal pathways in breast cancer stem cells and development of therapeutic pharmacological interventions. PI Mike Clarke, Stanford University. Project 2: Therapeutic targeting of CD47 on human leukemia and other cancer stem cells PI, Irv Weissman, Stanford University. Project 3: Microfluidic techniques for the molecular and functional analysis of gene expression, chromatin structure and in vitro culturing of cancer stem cells. PI Steve Quake, Stanford University. These projects are highly interconnected and reliant on each other for the success of the individual project as well as the success of this program. Each project will be supported by 4 cores: an administrative core, a bioinformatics core, an animal model core, and a flow cytometry core.