HNSCC: From Cancer Genomics to Personalized Biomarkers

2011年将出现超过50万新的头颈部鳞状细胞癌(HNSCC)病例， 包括美国的5万例，使其成为世界上第六大最常见的癌症。这些 癌症通常是致命的，五年存活率只有50%左右。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的，但这种药物不能 直接针对突变的肿瘤抑制基因，因为它们已经被灭活。考虑到缺乏 可用于HNSCC的靶向治疗、早期发现、监测和监测将是至关重要的 以降低与HNSCC相关的发病率和死亡率。这项提议的最终目标是 开发临床有用的生物标志物，可用于早期检测、监测、监测和 预后。为了实现这一目标，我们提出了一项详细的HNSCC基因分析(AIM#1)。这些 基因变化将用于开发和验证基于循环肿瘤DNA的生物标记物分析 HNSCC(目标2)。这些生物标记物将与未来的临床结果和结果相关。 研究(目标3)。上述研究将确定HNSCC的基因变化，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 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.