Novel Blood Assay for Lung Cancer Detection

描述（由申请人提供）：每年，近一百万例新的肺癌（LC）被诊断出来。在美国，据估计，2007年确定了约213，000例新病例（美国癌症协会）。在诊断后的两年内，这些患者中的大多数（约160，000）将死亡。这种疾病的诊断通常是在常规胸部X线和/或CT和MRI之后，并在活检和功能性（氟-18-标记脱氧葡萄糖）PET成像后得到证实。肺癌的治疗可能涉及手术、化疗和放射治疗以及更新的实验方法的组合。然而，肺癌患者的五年生存率约为15%，在过去几十年中没有变化。因此，迫切需要开发高度特异性、敏感性和准确性的方法来筛查和早期发现隐匿性疾病。 肿瘤起源于正常细胞的遗传和表观遗传改变的积累。这些转化的细胞获得新的“癌症特异性”分子指纹（DNA/RNA/蛋白质/脂质），使它们具有独特的表型。我们假设，在各种基于血液的肿瘤特异性特征测定中获得的假阳性率和假阴性率是相同的致命弱点的结果：它们都取决于从“健康”对照的血液获得的群体来源的平均特征谱，即基线/背景特征对被测试个体的基因组成不是特异性的。 在本申请中，我们提出（i）开发高度创新的基于WBC的测定，其（a）将准确预测动物中原发性和/或转移性LC病变的存在，并且（B）独立于“健康”对照的群体来源的平均特征;以及（ii）检查测定法检测肿瘤对治疗的反应以及在肿瘤被切除之前动物中LC的存在的能力。通过外部成像模式诊断。 我们预期基于WBC的血液测定最终将（i）以高特异性、灵敏度和准确性用于检测隐匿性肺肿瘤;（ii）使得能够在不知道患有该疾病或患有复发性疾病的个体中早期诊断肿瘤存在;（iii）将有意义的干预转移到肿瘤进展过程中更早的位置，从而预防转移性疾病的发展;（iv）监测肿瘤对常规（例如，手术、化疗）和实验性治疗;以及（v）允许肿瘤检测、诊断和治疗紧密结合（即，LC治疗的个性化）。

DESCRIPTION (provided by applicant): Every year, close to one million new cases of lung cancer (LC) are diagnosed. In the USA, it is estimated that approximately 213,000 new cases were identified in 2007 (American Cancer Society). Within two years of diagnosis, most of these patients (~160,000) will die. The diagnosis of this disease is usually subsequent to routine chest X-ray and/or CT and MRI and is confirmed upon biopsy and functional (fluorine-18-labeled deoxyglucose) PET imaging. Treatment of lung cancer can involve a combination of surgery, chemotherapy, and radiation therapy as well as newer experimental methods. However, the five-year survival rate of patients with lung cancer is approximately 15% and has not changed over the past several decades. Thus, it is imperative to develop highly specific, sensitive, and accurate methods for screening and early detection of occult disease. Tumors originate from normal cells upon the accumulation of genetic and epigenetic alterations. These transformed cells acquire new "cancer-specific" molecular fingerprints (DNA/RNA/protein/lipid) that give them unique phenotypes. We postulate that the false-positive and false-negative rates obtained in various blood-based, tumor-specific-signature assays are a consequence of the same Achilles' heel: they all depend on population-derived average signature profiles obtained from the blood of "healthy" controls, i.e. the baseline/background signature(s) is/are NOT specific to the genetic makeup of the individual being tested. In this application, we propose to (i) develop a highly innovative WBC-based assay that (a) will accurately predict the presence of primary and/or metastatic LC lesions in an animal, and (b) is independent of population-derived average signatures of "healthy" controls; and (ii) examine the capacity of the assay to detect the response of tumors to therapy as well as the presence of LC in animals before the tumors are diagnosed by external imaging modalities. We anticipate that the WBC-based blood assay eventually will (i) be useful in the detection of occult lung tumors with high specificity, sensitivity, and accuracy; (ii) enable the early diagnosis of tumor presence in individuals who are not known to have the disease or who have recurrent disease; (iii) move meaningful intervention to a much earlier position on the path of tumor progression, thereby forestalling the development of metastatic disease; (iv) monitor the response of tumors to routine (e.g., surgery, chemotherapy) and experimental treatment(s); and (v) allow tumor detection, diagnosis, and treatment to be closely coupled (i.e., personalization of LC therapy).