HNSCC: From Cancer Genomics to Personalized 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，五年存活率只有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、早期检测、监测和监控将是至关重要的 降低与HNSCC相关的发病率和死亡率。这项提案的最终目标是 开发临床上有用的生物标志物，可用于早期检测，监测，监视， 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。

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 worid. These cancers are frequentiy 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 moleculariy-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, eariy detection, monitoring, and surveillance will be critical to decrease the morbidity and mortality associated with HNSCC. The ultimate goal ofthis 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.