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

• 批准号: 10688908
• 负责人: CARTER VAN WAES
• 金额: $ 35.93万
• 依托单位: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
• 依托单位国家: 美国
• 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/10688908
• 关键词: Alcohols; Biological Markers; Cessation of life; Clinical; Cytology; Cytotoxic agent; Defect; Deglutition; Diagnosis; Disease; Drug Targeting; Early Diagnosis; Early treatment; FRAP1 gene; Gene Expression; Genetic; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Human Papillomavirus; Impairment; Investigation; Larynx; Malignant Neoplasms; Mediator of activation protein; Molecular; Multicenter Trials; NF-kappa B; Normal tissue morphology; Operative Surgical Procedures; Oral cavity; Pathogenesis; Pathway interactions; Patients; Pharyngeal structure; Play; Prevention; Prevention approach; Progressive Disease; Quality of life; RNA interference screen; Radiation; Recurrence; Recurrent disease; Reporter; Role; Signal Pathway; Signal Transduction; Speech; Squamous Epithelium; TNF gene; The Cancer Genome Atlas; Therapeutic; Voice; chemotherapy; genome-wide; irradiation; malignant phenotype; notch protein; novel strategies; response; side effect; targeted treatment; therapy resistant; tobacco exposure; transcription factor

As part of The Cancer Genome Atlas group characterizing head and neck cancer, we have identified components of the classical and alternative NF-kB, PI3K-mTOR, and Notch pathways as candidate genetic drivers for aberrant NF-kB activation and defects in death signaling. A multi-center trial targeting IAPs in the classical TNF-NF-kB pathway in combination with re-irradiation continues. Studies using a genome wide RNAi screen employing NF-kB reporter lines have identified potential drug targets promoting NF-kB activation, under investigation.

作为表征头颈癌的癌症基因组图谱组的一部分，我们已经确定了经典和替代NF-kB，PI 3 K-mTOR和Notch途径的组分作为异常NF-kB激活和死亡信号缺陷的候选遗传驱动因素。 靶向经典TNF-NF-kB途径中的IAP与再照射组合的多中心试验仍在继续。 使用基因组范围的RNAi筛选，采用NF-κ B报告细胞系的研究已经确定了促进NF-κ B激活的潜在药物靶点，正在研究中。

项目成果

Immunohistochemical analysis of NF-κB in human tumor tissue.

人类肿瘤组织中 NF-κB 的免疫组织化学分析。

• DOI: 10.1007/978-1-4939-2422-6_28
• 发表时间: 2015
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Allen,ClintT;VanWaes,Carter
• 通讯作者: VanWaes,Carter

Aberrant IKKα and IKKβ cooperatively activate NF-κB and induce EGFR/AP1 signaling to promote survival and migration of head and neck cancer.

• DOI: 10.1038/onc.2013.49
• 发表时间: 2014-02-27
• 期刊: Oncogene
• 影响因子: 8

CCR 20th anniversary commentary: Preclinical study of proteasome inhibitor bortezomib in head and neck cancer.

• DOI: 10.1158/1078-0432.ccr-14-2550
• 发表时间: 2015-03-01
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Allen CT;Conley B;Sunwoo JB;Van Waes C
• 通讯作者: Van Waes C

Attenuated TRAF3 Fosters Activation of Alternative NF-κB and Reduced Expression of Antiviral Interferon, TP53, and RB to Promote HPV-Positive Head and Neck Cancers.

• DOI: 10.1158/0008-5472.can-17-0642
• 发表时间: 2018-08-15
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Zhang J;Chen T;Yang X;Cheng H;Späth SS;Clavijo PE;Chen J;Silvin C;Issaeva N;Su X;Yarbrough WG;Annunziata CM;Chen Z;Van Waes C
• 通讯作者: Van Waes C

Nuclear NF-kappaB p65 phosphorylation at serine 276 by protein kinase A contributes to the malignant phenotype of head and neck cancer.

• DOI: 10.1158/1078-0432.ccr-09-1352
• 发表时间: 2009-10-01
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: Arun P;Brown MS;Ehsanian R;Chen Z;Van Waes C
• 通讯作者: Van Waes C