Field of Injury Based Biomarkers for Lung Cancer

基于损伤的肺癌生物标志物领域

• 批准号: 7748114
• 负责人: Jerome S Brody
• 金额: $ 27.79万
• 依托单位: ALLEGRO DIAGNOSTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-29 至 2010-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7748114
• 关键词: Algorithms; Biological; Biological Assay; Biological Markers; Boston; Breathing; Bronchoscopy; Cancer Etiology; Cell Line; Cessation of life; Characteristics; Clinical; Clinical Data; Confidence Intervals; Cost Savings; Country; Databases; Diagnosis; Diagnostic; Diagnostic Neoplasm Staging; Diagnostic Procedure; Diagnostic tests; Disease; Distal; Epithelial Cells; Evaluation; Event; Evidence Based Medicine; Funding; Gene Expression; Genes; Goals; Healthcare; Healthcare Systems; Injury; Intercept; International; Laboratories; Logistic Regressions; Logistics; Lung; Maintenance; Malignant Neoplasms; Malignant neoplasm of lung; Marketing; Measurement; Measures; Methodology; Methods; Mission; Modeling; Modification; Noise; Operative Surgical Procedures; Outcome; Patients; Phase; Physicians; Predictive Value; Price; Probability; Procedures; Process; Protocols documentation; RNA; Reagent; Reproducibility; Request for Proposals; Research Design; Research Project Grants; Risk; Running; Sampling; Screening procedure; Sensitivity and Specificity; Site; Small Business Innovation Research Grant; Smoker; Staging; Temperature; Testing; Third-Party Payer; Time; United States; Universities; Validation; base; cancer diagnosis; cell type; cigarette smoking; clinical Diagnosis; cohort; commercialization; computerized; cost; data integrity; health economics; high risk; improved; meetings; programs; public health relevance; sample collection; trend; trizol

DESCRIPTION (provided by applicant): This research project, presented as a "fast-track" SBIR proposal, deals with a new gene expression-based approach to the diagnosis and biological characterization of lung cancer in current and former smokers being evaluated for the possible diagnosis of lung cancer. Allegro Diagnostics is developing a portfolio of lung cancer biomarker products that are based on the principle that inhaled substances, cigarette smoke in particular, cause a "field of injury" throughout the lungs and airways, and that the global gene expression measured in easily accessible large airway epithelial cells obtained at bronchoscopy reflects biologic events occurring in the distal lung, where cancer develops. The first of these products, and the focus of this SBIR proposal, is BronchoGen, an 80 probe-set biomarker of lung cancer in current or former smokers. The immediate goals of the SBIR proposal are to evaluate the effect of new and improved reagents that have appeared in the past year on the BronchoGen test characteristics, to transfer the BronchoGen test to a commercial laboratory from the academic laboratory in which it was developed, and are to further validate the biomarker's accuracy, sensitivity, and specificity in a sample of 400 patients. The ultimate product of these studies will be a CLIA-approved lung cancer biomarker that will be submitted for FDA approval. Multiple sites throughout the country and two high-volume international sites will provide samples of bronchial epithelial cells from patients in whom bronchoscopy is being done to evaluate the possibility that a patient has lung cancer. Airway epithelial cell samples will be placed in a new RNA preservative that is effective when stored at room temperature for several weeks, sent by Federal Express to a commercial laboratory specializing in gene expression array studies, and CEL file results transported to Allegro Diagnostics for analysis and correlation with a computerized database that stores important clinical data, including ultimate diagnosis, the clinical process of diagnostic evaluation, staging of the cancer (if present), cell type and ultimate outcome. The initial product of these studies, BronchoGen", will reduce the costs and risks of unnecessary diagnostic procedures diagnosis, and risks of invasive procedures, and the amount of time between the suspicion of lung cancer and cancer diagnosis, by avoiding additional diagnostic procedures that often occur after non-diagnostic bronchoscopy. With BronchoGen", physicians will receive a lung cancer 'present or absent' statement, together with a statistical explanation of the biomarkers positive and negative predictive value and accuracy and sensitivity. The project goals of developing more timely and accurate diagnostics for lung cancer are directly aligned with NCI's mission to reduce the burden and eliminate adverse outcomes of cancer. PUBLIC HEALTH RELEVANCE: Allegro Diagnostics is developing a "toolbox" of products focused on the diagnosis and treatment of lung cancer, the leading cause of cancer death in the United States and the world. The focus of this SBIR, and the 1st of these products, is BronchoGen, a gene-expression based biomarker for use in patients undergoing bronchoscopy for the diagnosis of lung cancer. BronchoGen will decrease the amount of time between suspicion of lung cancer and lung cancer diagnosis, and will reduce the costs of diagnosis, treatment, and screening programs in people at high risk for the disease.

描述（由申请人提供）：本研究项目作为“快速通道”SBIR提案提出，涉及一种新的基于基因表达的方法，用于诊断当前和既往吸烟者肺癌的生物学特征，以评估肺癌的可能诊断。Allegro Diagnostics正在开发一系列肺癌生物标志物产品，这些产品基于以下原理：吸入的物质，特别是香烟烟雾，会在整个肺部和气道中造成“损伤区域”，并且在支气管镜检查中获得的易接近的大气道上皮细胞中测量的全局基因表达反映了发生在远端肺部的生物事件，癌症就是在那里发生的。这些产品中的第一个，也是SBIR提案的重点，是BronchoGen，这是目前或以前吸烟者肺癌的80个探针集生物标志物。SBIR提案的直接目标是评估过去一年中出现的新的和改进的试剂对BronchoGen测试特性的影响，将BronchoGen测试从开发它的学术实验室转移到商业实验室，并进一步验证生物标志物的准确性，灵敏度和特异性在400名患者的样本中。这些研究的最终产品将是CLIA批准的肺癌生物标志物，将提交FDA批准。全国各地的多个研究中心和两个高容量的国际研究中心将提供来自正在接受支气管镜检查的患者的支气管上皮细胞样本，以评估患者患有肺癌的可能性。将气道上皮细胞样本置于新的RNA防腐剂中，该防腐剂在室温下储存数周时有效，通过联邦快递发送至专门从事基因表达阵列研究的商业实验室，并将CEL文件结果运送至Allegro Diagnostics进行分析并与计算机化数据库进行关联，该数据库存储重要的临床数据，包括最终诊断、诊断评估的临床过程、癌症分期（如果存在）、细胞类型和最终结果。这些研究的初始产品“BronchoGen”将通过避免非诊断性支气管镜检查后经常发生的额外诊断程序，降低不必要的诊断程序诊断的成本和风险，以及侵入性程序的风险，以及怀疑肺癌和癌症诊断之间的时间量。使用BronchoGen”，医生将收到肺癌“存在或不存在”的声明，以及生物标志物阳性和阴性预测值以及准确性和灵敏度的统计解释。开发更及时和准确的肺癌诊断方法的项目目标与NCI减轻负担和消除癌症不良后果的使命直接一致。公共卫生相关性：Allegro Diagnostics正在开发一个专注于肺癌诊断和治疗的产品“工具箱”，肺癌是美国和世界上癌症死亡的主要原因。该SBIR的重点是BronchoGen，这是一种基于基因表达的生物标志物，用于接受支气管镜检查的患者诊断肺癌。BronchoGen将减少怀疑肺癌和肺癌诊断之间的时间，并将降低诊断，治疗和筛查项目的成本。