Lung Cancer Mutation Analysis

肺癌突变分析

• 批准号: 7944145
• 负责人: PAUL A. BUNN
• 金额: $ 234.53万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 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 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7944145
• 关键词: Accounting; Adenocarcinoma; BRAF gene; Cancer Etiology; Cancer Patient; Cessation of life; Classification; Clinical; Clinical Trials; Clinical Trials Network; Combination Drug Therapy; Data; Development; Disease; ERBB2 gene; ERBB3 gene; Enrollment; Epidermal Growth Factor Receptor; Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor; Equipment; ErbB4 gene; Europe; Excision; Frequencies; Funding; Funding Agency; Future; Genes; Genetic screening method; Genomics; Goals; Grant; Institution; KRAS2 gene; Laboratories; Lead; Link; Lung Adenocarcinoma; MAP2K1 gene; Malignant Neoplasms; Malignant neoplasm of lung; Medicine; Methods; Molecular; Mutate; Mutation; Mutation Analysis; Non-Small-Cell Lung Carcinoma; Oncogenes; Online Systems; Operative Surgical Procedures; Oral; Outcome; PIK3CA gene; Pathologic; Pathology; Patients; Positioning Attribute; Progression-Free Survivals; Protocols documentation; Radiation therapy; Reagent; Research; Research Infrastructure; Series; Signal Pathway; Specimen; Staging; Testing; Therapeutic Agents; Therapy Clinical Trials; Time; Tissue Banks; Tissues; Toxic effect; Tumor Tissue; Woman; abstracting; advanced disease; base; cancer genomics; chemotherapy; cost; experience; fusion gene; genetic analysis; inhibitor/antagonist; interest; intravenous administration; meetings; member; men; new technology; novel; novel therapeutics; operation; outcome forecast; prognostic; prototype; response; tumor

DESCRIPTION (provided by applicant): Abstract this project aims to establish a Lung Cancer Mutation Consortium (LCMC) consisting of 13 institutions with a major interest in lung cancer and genomic testing of lung cancer as documented by having major NCI grants in lung cancer. The LCMC members will collect linked clinical, pathologic and genomic data on 1000 patients with advanced adenocarcinoma of the lung in the proposed clinical trial. The genomic tests will be conducted in CLIA certified laboratories located at consortium institutions according to consortium protocols. The protocol will determine the frequency of each genetic change; the association between the genetic change, the clinical features, and the outcome; and the association between different genetic changes. The information will be used to validate and/or change the pathologic sub-classification of adenocarcinomas. The genetic analyses will be used to determine if patients with specific genetic changes are eligible for enrollment into therapeutic trials evaluating novel targeted therapies directed at the specific mutation / amplification / fusion gene. These therapeutic trials are funded by other mechanisms. The proposal will lead to the creation of at least 16 new positions and to the purchase of equipment and reagents for the genetic testing. The trial results and the establishment of the LCMC will hasten the implementation of personalized medicine for lung cancer. PUBLIC HEALTH RELEVANCE: Relevance Lung cancer is the leading cause of cancer death in men and women in the U.S., accounting for about 30% of all cancer deaths. About half of all lung cancer patients present with advanced disease for which standard chemotherapy combinations produce only modest survival improvement with the associated high toxicity rates, inconvenience of intravenous administration and high costs. Recent molecular studies showed that as many as 50% of lung cancer have activating mutations in known oncogenes to which novel therapeutic agents have been developed. Early clinical trials suggest that targeted oral agents have less toxicity and greater benefit than chemotherapy but only when administered to patients with the specific mutated oncogene. The new technologies in this application will allow a large number of lung cancer patients to have molecular tests for these newly described oncogenes so that we can understand their frequency, relevance and importance as predictors to benefit from the new targeted agents. This proposal will hasten the development of personalized medicine for lung cancer and other cancers as well.

描述（由申请人提供）：摘要该项目旨在建立一个肺癌突变联盟（LCMC），该联盟（LCMC）由13个机构组成，对肺癌和肺癌的基因组测试主要兴趣，这是通过在肺癌中拥有大量NCI补助的肺癌。 LCMC成员将在拟议的临床试验中收集1000例肺晚期腺癌患者的临床，病理和基因组数据。基因组测试将根据财团方案在联盟机构的CLIA认证实验室进行。该方案将确定每个遗传变化的频率；遗传变化，临床特征和结果之间的关联；以及不同遗传变化之间的关联。该信息将用于验证和/或更改腺癌的病理亚分类。遗传分析将用于确定特定遗传变化的患者是否有资格参加评估针对特定突变 /扩增 /融合基因的新型靶向疗法的治疗试验。这些治疗试验由其他机制资助。该提案将导致至少创建16个新职位，并为基因测试购买设备和试剂。试验结果和LCMC的建立将加速为肺癌实施个性化医学。 公共卫生相关性：相关性肺癌是美国男性和女性癌症死亡的主要原因，约占所有癌症死亡的30％。在所有肺癌患者中，大约一半的患者患有晚期疾病，标准化疗组合仅与相关的高毒性率，静脉内给药和高成本相关的高毒性率，造成适度的生存改善。最近的分子研究表明，多达50％的肺癌在已开发了新型治疗剂的已知癌基因中具有激活突变。早期的临床试验表明，靶向口服剂的毒性和益处更低，但仅在对患有特定突变癌基因的患者进行给药时。本应用中的新技术将使大量的肺癌患者对这些新描述的癌基因进行分子测试，以便我们可以理解它们的频率，相关性和重要性，作为从新靶向药物中受益的预测因子。该建议还将加快针对肺癌和其他癌症的个性化医学的开发。