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Targeting fascin to block tumor metastasis

靶向肌成束蛋白阻断肿瘤转移

基本信息

批准号：
9191345
负责人：
Xin-Yun Huang
金额：
$ 38.62万
依托单位：
WEILL MEDICAL COLL OF CORNELL UNIV
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-08 至 2020-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9191345
关键词：
Actins Adult Adverse effects Affect Animal Model Animals Area Binding Binding Sites Biochemical Biological Biological Process Blood Circulation Bundling Cancer Patient Cause of Death Cell Shape Cell membrane Cells Cessation of life Chemicals Clinical Complex Crystallization Cytoskeleton Development Dimensions Disseminated Malignant Neoplasm Distant Down-Regulation Drug Kinetics Embryo Embryonic Development Epithelial Cells Extravasation Failure Filament Filopodia Financial compensation Fright Human In Vitro Individual Knockout Mice Malignant Neoplasms Mammary Neoplasms Membrane Microfilaments Modification Molecular Conformation Mus Mutagenesis Neoplasm Metastasis Organ Pharmaceutical Preparations Phenotype Polymers Primary Neoplasm Process Proteins RNA Interference Radiation Roentgen Rays Secondary to Site Structure Study models Survival Rate Testing Therapeutic Tissues Toxic effect Tumor Cell Invasion Tumor Cell Migration Tumor-Associated Process analog base cancer recurrence cancer therapy capillary bed cell motility chemotherapy curative treatments electron tomography experimental study fascin flexibility improved inhibitor/antagonist knockout gene metastatic process mouse model mutant outcome forecast public health relevance reconstitution small molecule small molecule inhibitor small molecule libraries targeted treatment therapeutic target tumor

项目摘要

DESCRIPTION (provided by applicant): Tumor metastasis is the major cause of death in cancer patients. Thus, blocking tumor metastasis will significantly increase the survival rate of cancer patients and allow more moderate radiation or chemotherapy with less side-effects. One critical step of tumor metastasis is tumor cell migration and invasion. In this application, we focus on fascin, an actin-bundling protein, which is critical for tumor invasion and metastasis. Elevated expression of fascin is correlated with poor prognosis and short survival in cancer patients. In specific aim 1, we will investigate the mechanism of action of fascin inhibitors. In specific aim 2, we will further optimize fascin inhibitors. In specific aim 3, we will use animal models to examine the efficacy and toxicity of optimized fascin inhibitors.

描述(申请人提供)：肿瘤转移是癌症患者死亡的主要原因。因此，阻断肿瘤转移将显著提高癌症患者的存活率，并允许更多的适度放疗或化疗，而副作用更少。肿瘤转移的关键步骤之一是肿瘤细胞的迁移和侵袭。在这一应用中，我们重点介绍了一种肌动蛋白捆绑蛋白，它对肿瘤的侵袭和转移至关重要。在癌症患者中，Fascin的高表达与预后不良和生存期短有关。在特定的目标1中，我们将研究Fascin抑制剂的作用机制。在具体目标2中，我们将进一步优化法菌素抑制剂。在具体目标3中，我们将使用动物模型来检测优化的法辛抑制剂的疗效和毒性。