Development of a Four-Class, Molecular Subtyping Diagnostic for HPV-negative Head and Neck Cancer

开发 HPV 阴性头颈癌的四类分子亚型诊断方法

基本信息

批准号：
10216187
负责人：
David N Hayes
金额：
$ 49.78万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2023-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10216187
关键词：
Address Anatomy Biological Biological Assay Cells Cessation of life Characteristics Clinic Clinical Clinical Data Clinical Management Clinical Markers Collaborations Combined Modality Therapy Data Data Set Decision Making Development Diagnostic Diagnostic radiologic examination Etiology Exhibits Formalin Gene Expression Genes Genomics Goals Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Histologic Human Papillomavirus Immune response Incidence Individual Industry Collaboration Knowledge Laboratories Laryngeal Squamous Cell Carcinoma Larynx Lymph Node Dissections Malignant Neoplasms Malignant neoplasm of larynx Manufacturer Name Marketing Mesenchymal Modality Molecular Mutation Neck Dissection Neoplasm Metastasis Nodal North Carolina Operative Surgical Procedures Oral Stage Oropharyngeal Outcome Paraffin Embedding Patient Care Patient-Focused Outcomes Patients Pharmacologic Substance Pharyngeal structure Population Production Prognosis Public Health Radiation Radiation therapy Research Risk Risk Management Sampling Selection for Treatments Stratification The Cancer Genome Atlas Therapeutic Tissue Embedding Tobacco Tobacco use Translating Treatment Failure Tumor Subtype Tumor stage United States Work base cancer care cancer genomics cancer subtypes chemotherapy clinically relevant common treatment design detection assay diagnostic assay drug development gene panel genetic signature genomic biomarker high risk hypopharynx improved in-vitro diagnostics interest malignant mouth neoplasm malignant oropharynx neoplasm molecular marker molecular modeling molecular subtypes mouth squamous cell carcinoma novel personalized diagnostics personalized medicine predicting response predictive test prognostic prognostic assays radiation resistance radiation response risk stratification socioeconomics statistics support tools transcriptome transcriptome sequencing treatment responders treatment response treatment strategy tumor tumor registry

项目摘要

Abstract: Head and neck squamous cell carcinoma (HNSCC), including cancers of the oral cavity, pharynx, and larynx, is the sixth most common cancer worldwide worldwide. In the United States, approximately 60,000 new cases of HNSCC and 12,000 deaths are projected for 2015. A growing body of evidence demonstrates increasing incidence of oropharyngeal cancers, including a subset of human papillomavirus (HPV) associated tumors that demonstrate better prognosis. Despite the recent research interest in HPV-positive HNSCC, HPV-negative tobacco-associated cases continue to comprise the vast majority of HNSCC. Particularly in our state of North Carolina, where the population is more racially and socioeconomically diverse and where tobacco use remains high, HPV-negative HNSCC remains a significant public health problem. Oncologic outcomes for HPV-negative HNSCC remain poor and have not improved in the last 50 years, and there is a need to identify novel, personalized diagnostics and treatment strategies for patients with HPV-negative HNSCC. Four intrinsic HNSCC gene expression subtypes (basal (BA), classical (CL), mesenchymal (MS) and atypical (AT)) have been described, and provide an opportunity to inform patient management. These subtypes exhibit distinct differences in cell of origin, tumor drivers, proliferation, prognosis, and host immune response. In this application, we intend to develop and validate a clinic-ready diagnostic for HPV-negative HNSCC that includes both prognostic and predictive applications. While several therapeutic options exist for HNSCC including surgery, radiation therapy, and, chemotherapy, treatment selection remains empiric. With the exception of HPV status in oropharyngeal cancer, the molecular characteristics of individual tumors are generally not taken into account when deciding on treatment. This academic/industry collaboration will provide prognostic information based on biologic gene expression subtypes to guide decision-making for HPV-negative HNSCC, such as application of more aggressive surgery or radiation therapy based on tumor characteristics. We hypothesize that development efforts as described in this application will lead to a clinic-ready subtyping diagnostic, that combined with other mutation and clinical data, will provide both prognostic and predictive applications to guide the management of HNSCC.

抽象的：头部和颈部鳞状细胞癌（HNSCC），包括口腔癌，咽和 Larynx是全球第六个最常见的癌症。在美国，大约有60,000 预计2015年HNSCC的新病例和12,000例死亡。口咽癌的发生率增加，包括人乳头瘤病毒的子集（HPV）相关的肿瘤表现出更好的预后。尽管最近对HPV阳性的研究兴趣 HNSCC，HPV阴性烟草相关的病例继续构成了绝大多数HNSCC。特别是在我们的北卡罗来纳州，在种族和社会经济上，人口更加 HPV阴性HNSCC的多样性和烟草使用率仍然很高，仍然是重要的公共卫生问题。 HPV阴性HNSCC的肿瘤学结果仍然很差，在过去的50个多年，有必要为患者确定新颖的个性化诊断和治疗策略与HPV阴性HNSCC。四个固有的HNSCC基因表达亚型（基础（BA），经典（CL），，已经描述了间充质（MS）和非典型（AT）），并提供了一个机会，以告知患者管理。这些亚型在起源细胞，肿瘤驱动因素，增殖中表现出明显差异，预后和宿主免疫反应。在此应用程序中，我们打算开发和验证诊所就绪 HPV阴性HNSCC的诊断，包括预后和预测应用。尽管 HNSCC存在几种治疗选择，包括手术，放射治疗以及化学疗法，治疗选择仍然是经验性的。除了口咽癌中的HPV状态外，决定时通常不考虑单个肿瘤的分子特征治疗。这种学术/行业的合作将提供基于生物学基因的预后信息表达亚型用于指导HPV阴性HNSCC的决策，例如应用更多基于肿瘤特征的侵略性手术或放射治疗。我们假设这一发展本应用程序中所述的努力将导致诊所就绪的亚型诊断，并结合其他突变和临床数据将提供预后和预测应用，以指导 HNSCC的管理。