Head and Neck squamous cell carcinoma radiation response modulation by HPV

HPV 调节头颈鳞状细胞癌放射反应

基本信息

批准号：
8604213
负责人：
RANDALL J KIMPLE
金额：
$ 23.41万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-03-01 至 2016-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8604213
关键词：
Age Alcohols Apoptotic Award Biological Models Biology Cell Line Cell physiology Cells Clinical Clinical Research Clinical Trials Complex Conflict (Psychology)Development Disease Down-Regulation EGFR Protein Overexpression Epidermal Growth Factor Receptor Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Family member Future Genes Goals Grant Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Human Human Papillomavirus Human papilloma virus infection Incidence Ionizing radiation JUN gene Lead Learning Link Malignant Epithelial Cell Malignant Neoplasms Mediating Membrane Proteins Mentors Molecular Molecular Virology Outcome Pathway interactions Patients Phase Play Primary Neoplasm Principal Investigator Protein p53 Protein phosphatase Proteins Public Health Radiation Radiation Tolerance Radiation-Sensitizing Agents Radiosensitization Receptor Inhibition Receptor Signaling Reporting Research Role Scaffolding Protein Signal Pathway Staging Techniques Tobacco Toxic effect Training Transgenic Mice Transgenic Model Tumor Suppressor Proteins Up-Regulation Viral Genes Viral Proteins Virus Diseases Work abstracting base career development cdc Genes chemoradiation chemotherapy clinical care design effective therapy experience genetic profiling improved member mouse model next generation novel outcome forecast patient population programs protein expression receptor expression response therapy development treatment response trial comparing tumor tumor xenograft virology

项目摘要

Project Summary/Abstract Human papillomavirus (HPV) associated head and neck cancer is a growing public health concern. These patients commonly present at a younger age and with more advanced stage disease than patients with traditional tobacco and alcohol associated head and neck squamous cell carcinoma (HNSCC). Paradoxically, these HPV-associated tumors show notably improved survival outcomes. Mechanisms underlying these improved outcomes remain unclear. The work proposed in this Pathways to Independence Award has two primary goals: 1) to facilitate career development of the principal investigator (PI) and to help establish his independence to lead a research program investigating radiation response in virally associated cancers; and, 2) to understand how HPV-associated HNSCC differs from traditional HNSCC in response to radiation and chemotherapy. During the mentored phase of research, the PI will obtain additional training in molecular virology, human papillomavirus biology, and mouse models of cancer. The research conducted during the mentored phase will examine why HPV-associated HNSCC are more sensitive than traditional HNSCC to radiation and chemotherapy and to examine the ability of epidermal growth factor receptor (EGFR) inhibitors to sensitize HPV-associated head and neck cancer to radiation despite low levels of EGFR expression. During the independent phase, research will examine the impact of HPV viral proteins on EGFR inhibitor-mediated radiosensitization and the impact of EGFR loss on radiosensitization strategies. These studies will provide new clues regarding mechanisms of increased sensitivity to radiation and chemotherapy and may identify important new targets for therapy development to further improve outcome for patients with both HPV-associated and non-HPV-associated head and neck cancer.

项目摘要/摘要人乳头瘤病毒（HPV）相关的头颈癌是日益增长的公共卫生问题。这些患者通常在年龄较小，患有更晚期疾病的患者比患者传统的烟草和酒精相关的头和颈部鳞状细胞癌（HNSCC）。矛盾的是，这些与HPV相关的肿瘤显示出显着改善的生存结果。这些机制改善的结果尚不清楚。在此独立奖项奖中提出的工作有两个主要目标：1）促进主要研究人员（PI）的职业发展并帮助建立他的独立性领导一项研究计划，研究病毒相关的癌症中的辐射反应；和， 2）了解HPV相关的HNSCC与传统的HNSCC有何响应和传统HNSCC的不同化学疗法。在指导的研究阶段，PI将获得分子的额外培训病毒学，人乳头瘤病毒生物学和癌症小鼠模型。在指导阶段将研究为什么HPV相关的HNSCC比传统的HNSCC更敏感放射和化学疗法，并检查表皮生长因子受体（EGFR）抑制剂对尽管EGFR表达较低，但将HPV相关的头颈癌敏感到辐射。期间独立阶段，研究将研究HPV病毒蛋白对EGFR抑制剂介导的影响放射敏化和EGFR损失对放射敏化策略的影响。这些研究将提供新的关于提高辐射和化学疗法敏感性的机制的线索，并可能确定重要治疗开发的新靶标，以进一步改善与HPV相关和非HPV相关的头颈癌。