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NF-kappaB in pathogenesis and therapy of head and neck cancer

NF-κB 在头颈癌发病机制和治疗中的作用

基本信息

批准号：
9147422
负责人：
CARTER VAN WAES
金额：
$ 54.25万
依托单位：
NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/9147422
关键词：
Adverse effects Alcohols Apoptosis Biological Markers Bortezomib Carcinoma Cell Survival Cessation of life Clinical Clinical Trials Cyclic AMP-Dependent Protein Kinases Cytotoxic Chemotherapy Cytotoxic agent Data Analyses Defect Deglutition Development Diagnosis Drug Targeting Early Diagnosis Early treatment Epithelial Exposure to Family Gene Expression Gene Targeting Genetic Goals Growth Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Hereditary Disease Human Papillomavirus Infection Inflammation Investigation Laboratories Larynx MAP Kinase Gene MAP3K7 gene Malignant Neoplasms Mediator of activation protein Molecular Target Mutation NF-kappa B Neoplasm Metastasis Normal tissue morphology Nuclear Oncogenes Oral cavity Pathogenesis Pathway interactions Patients Pharmaceutical Preparations Pharyngeal structure Phosphotransferases Play Prevention Prevention approach Prevention therapy Progressive Disease Proteasome Inhibition Proteasome Inhibitor Protein Kinase Quality of life RNA Interference Radiation Radiosurgery Recurrence Recurrent disease Reporter Resistance Role STAT3 gene Safety Schedule Serum Signal Pathway Signal Transduction Sirolimus Speech TNF gene The Cancer Genome Atlas Therapeutic Tobacco Toxic effect Transactivation Transcription Factor AP-1 Voice activating transcription factor angiogenesis chemotherapy cytokine cytotoxic cytotoxicity genome-wide human study improved inhibitor/antagonist mTOR Inhibitor malignant phenotype multicatalytic endopeptidase complex novel strategies p65 preclinical study radiosensitizing response response to injury targeted treatment therapy resistant tumor

项目摘要

NF-kappaB includes a family of signal-activated transcription factors that normally regulate responses to injury and infection but which are aberrantly activated in many carcinomas. Cumulative evidence implicates NF-kappaB in cell survival, inflammation, angiogenesis, spread and therapeutic resistance during tumor development, progression and metastasis of carcinomas. Non-specific natural and synthetic agents that inhibit NF-kappaB have demonstrated activity and safety in prevention or therapy. NF-kappaB-activating kinases are under investigation for targeted prevention and therapy of carcinoma. As part of The Cancer Genome Atlas group characterizing head and neck cancer, we have identified components of PI3K and TNF pathway as candidate genetic drivers for aberrant NF-kB activation and defects in death signaling. A clinical trial with mTOR inhibitor rapamycin has completed accrual and is under data analysis. Studies using a genome wide RNAi screen employing NF-kB reporter lines have identified potential drug targets promoting NF-kB activation.

NF-κ B包括一个信号激活的转录因子家族，通常调节对损伤和感染的反应，但在许多癌中被异常激活。累积的证据表明NF-κ B在肿瘤发展、进展和癌转移过程中参与细胞存活、炎症、血管生成、扩散和治疗抗性。抑制NF-κ B的非特异性天然和合成试剂已证明在预防或治疗中的活性和安全性。NF-κ B激活激酶正在研究用于癌症的靶向预防和治疗。作为表征头颈癌的癌症基因组图谱组的一部分，我们已经鉴定了PI 3 K和TNF途径的组分作为异常NF-kB活化和死亡信号传导缺陷的候选遗传驱动因子。mTOR抑制剂雷帕霉素的临床试验已完成招募，正在进行数据分析。使用采用NF-κ B报告细胞系的全基因组RNAi筛选的研究已经鉴定了促进NF-κ B活化的潜在药物靶标。