HNSCC: From Cancer Genomics to Personalized Biomarkers

HNSCC：从癌症基因组学到个性化生物标志物

• 批准号: 9133128
• 负责人: Nishant Agrawal
• 金额: $ 35.29万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9133128
• 关键词: Biological Assay; Biological Markers; Breathing; Clinical; Cosmetics; DNA; Deformity; Deglutition; Development; Disease; Early Diagnosis; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Feces; Gene Rearrangement; Generations; Goals; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Hearing; Human; Malignant Neoplasms; Molecular; Monitor; Morbidity - disease rate; Mutate; Mutation; Oncogenes; Operative Surgical Procedures; Outcome; Pathogenesis; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Phonation; Plasma; Point Mutation; Prospective Studies; Radiation therapy; Recurrence; Recurrent disease; Reproduction spores; Saliva; Salivary; Smell Perception; Somatic Mutation; Speech; Taste Perception; Testing; Tumor Burden; Tumor Suppressor Genes; United States; Validation; Work; base; burden of illness; cancer genome; cancer genomics; chemotherapy; clinical biomarkers; digital; functional disability; genetic analysis; genome sequencing; mortality; new therapeutic target; outcome forecast; specific biomarkers; targeted treatment; treatment response; tumor; tumor DNA; whole genome

More than half a million new cases of head and neck squamous cell carcinoma (HNSCC) will occur in 2011, including 50,000 cases in the United States, making it the sixth most common cancer in the world. These cancers are frequently lethal, with a five-year survival of only ~50%. Our group found that HNSCC is characterized by tumor suppressor gene predominance. This distinction is critical because the new generation of molecularly-targeted therapies is directed toward activated oncogenes but such drugs cannot directly target mutated tumor suppressor genes because they are already inactivated. Given the lack of targeted therapies that are available for HNSCC, early detection, monitoring, and surveillance will be critical to decrease the morbidity and mortality associated with HNSCC. The ultimate goal of this proposal is to develop clinically useful biomarkers that can be used for early detection, monitoring, surveillance, and prognosis. To achieve this goal, we propose a detailed genetic analysis of HNSCC (AIM #1). These genetic changes will be used to develop and validate circulating tumor DNA based biomarker assay in HNSCC (Aim #2). The biomarkers will be con-elated with clinical findings and outcomes in a prospective study (Aim #3). The above studies will identify genetic changes in HNSCC and allow the development of clinically useful biomarkers.

2011年将有50多万头颈部鳞状细胞癌（HNSCC）新发病例， 包括美国的50，000例病例，使其成为世界上第六大常见癌症。这些 癌症通常是致命的，五年存活率仅为~ 50%。我们小组发现HNSCC是 以肿瘤抑制基因占优势为特征。这一区别至关重要，因为新的 分子靶向疗法的产生是针对激活的癌基因，但这些药物不能 直接靶向突变的肿瘤抑制基因，因为它们已经失活。由于缺乏 HNSCC的靶向治疗、早期发现、监测和监控将至关重要 降低与HNSCC相关的发病率和死亡率。这项建议的最终目的是 开发临床上有用的生物标志物，可用于早期检测，监测，监视， 预后为了实现这一目标，我们提出了一个详细的遗传分析HNSCC（AIM #1）。这些 遗传变化将用于开发和验证基于循环肿瘤DNA的生物标志物测定， HNSCC（目标#2）。这些生物标志物将与临床发现和前瞻性结局相关。 研究（目标#3）。上述研究将确定HNSCC的遗传变化，并允许开发 临床上有用的生物标志物。