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.

超过50万例头颈部鳞状细胞癌（HNSCC）将在2011年发生， 在美国包括50,000例病例，使其成为世界上第六大癌症。这些 癌症经常致命，五年生存率仅约50％。我们的小组发现HNSCC是 以肿瘤抑制基因占主导地位为特征。这种区别至关重要，因为新的 分子靶向疗法的产生针对激活的癌基因，但这种药物不能 直接靶向突变的肿瘤抑制基因，因为它们已经被灭活。鉴于缺乏 可用于HNSCC，早期检测，监测和监视的有针对性疗法至关重要 降低与HNSCC相关的发病率和死亡率。该提议的最终目标是 开发临床上有用的生物标志物，可用于早期检测，监测，监视和 预后。为了实现这一目标，我们提出了对HNSCC的详细遗传分析（AIM＃1）。这些 遗传变化将用于开发和验证基于肿瘤DNA的生物标志物测定法 HNSCC（AIM＃2）。生物标志物将与预期的临床发现和结果相关 研究（目标＃3）。以上研究将确定HNSCC的遗传变化，并允许发展 临床上有用的生物标志物。