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.

项目概要/摘要人乳头瘤病毒 (HPV) 相关的头颈癌是一个日益严重的公共卫生问题。这些与患有以下疾病的患者相比，患者的发病年龄通常更年轻且处于晚期疾病阶段传统的烟草和酒精相关的头颈鳞状细胞癌（HNSCC）。自相矛盾的是，这些 HPV 相关肿瘤的生存结果显着改善。这些背后的机制改善结果仍不清楚。本次独立之路奖提出的作品有两项主要目标：1）促进首席研究员（PI）的职业发展并帮助建立他的独立领导一项调查病毒相关癌症辐射反应的研究计划；和， 2) 了解 HPV 相关 HNSCC 在对辐射的反应方面与传统 HNSCC 有何不同化疗。在研究的指导阶段，PI 将获得分子方面的额外培训病毒学、人乳头瘤病毒生物学和小鼠癌症模型。期间进行的研究指导阶段将研究为什么 HPV 相关的 HNSCC 比传统的 HNSCC 对放疗和化疗，并检查表皮生长因子受体 (EGFR) 抑制剂的能力尽管 EGFR 表达水平较低，但仍使 HPV 相关头颈癌对辐射敏感。期间独立阶段，研究将检查 HPV 病毒蛋白对 EGFR 抑制剂介导的影响放射增敏以及 EGFR 丢失对放射增敏策略的影响。这些研究将提供新的有关放射和化疗敏感性增加机制的线索，并可能确定重要的治疗开发的新目标，以进一步改善 HPV 相关和 HPV 患者的治疗结果非 HPV 相关的头颈癌。