ECOG-ACRIN Thoracic Malignancies Integrated Translational Science Center

描述(申请人提供)：随着新的分子靶点的确定和个性化治疗方案的发展，肺癌的治疗进入了一个新的时代。对于有特定分子异常的患者，靶向治疗可显著改善肿瘤反应和疾病控制持续时间。然而，治疗出现了抗药性，治愈方法仍然难以捉摸。需要新的方法来改善这些患者的预后。为了实现这一点，我们需要确定新的方法来监测患者对特定靶向治疗的耐药性的发展。另一个研究领域涉及开发新的生物标记物，以确定有复发风险或对特定治疗剂敏感的患者。基因组学、表观遗传学和蛋白质组学领域的新发展允许将这些技术应用于国家临床试验网络(NCTN)最近进行的和新的临床试验的患者样本。ECOG-ACRIN小组打算建立一个主要关注胸部恶性肿瘤的转化科学中心，以开发治疗肺癌的新方法，并开发新的生物标记物，随后可以在未来的临床试验中进行测试。胸恶性肿瘤综合翻译科学中心的主要目标是：1.开发基因组、表观基因组和蛋白质组学方法，以加强正在进行和计划中的ECOG-ACRIN研究中的生物标记物发现工作；2.对现有的肺癌肿瘤标本进行试点研究，这将导致基于生物标志物的预期临床试验；以及3.在ECOG-ACRIN胸科委员会进行的临床试验中，快速翻译试点项目的结果和生物标志物发现工作。在拟议的试点项目中，突出的包括利用血浆DNA样本来识别目标癌症突变，评估新的表观遗传学标记物来预测早期肺癌患者的复发风险，研究LKB1突变对早期肺癌预后的影响，以及测试克服靶向治疗耐药性的新方法。 相关性：这项提案将研究新的翻译策略以改善肺癌的预后。该中心将专注于生物标记物的发现、使用外周血检测显性致癌突变的新方法、克服靶向治疗耐药性的新策略，并将尝试在正在进行的和计划中的ECOG-ACRIN临床试验中验证这些发现。

DESCRIPTION (provided by applicant): The treatment of lung cancer has entered a new era with the identification of new molecular targets and the development of individualized treatment options. For patients with specific molecular abnormalities, targeted therapies result in robust improvements in tumor response and disease control duration. However, resistance to therapy occurs and a cure remains elusive. New approaches are needed to improve outcomes for these patients. In order to accomplish this, we need to identify novel methods to monitor patients for development of resistance with regards to specific targeted therapies. Another area of research involves developing new biomarkers to identify patients at risk for recurrence or sensitivity to specific therapeutic agents. New developments in the area of genomics, epigenetic and proteomics allow for application of these technologies in patients specimens from recent and new clinical trials conducted by the National Clinical Trials Network (NCTN). The ECOG-ACRIN group intends to establish a Translational Science Center that has a primary focus on thoracic malignancies to develop novel approaches to treat lung cancer and to develop new biomarkers that can subsequently be tested in prospective clinical trials. The main objectives of the Thoracic Malignancies Integrated Translational Science Center are: 1. To develop genomic, epigenomic and proteomics approaches to enhance biomarker discovery efforts in ongoing and planned ECOG-ACRIN studies; 2. To conduct pilot studies on existing lung cancer tumor specimens that will lead to prospective biomarker-based clinical trials; and 3. To rapidly translate the findings of the pilot projects and biomarker discovery efforts in clinical trials conducted by the ECOG-ACRIN Thoracic Committee. Salient among the proposed pilot projects include utilizing plasma DNA specimens to identify target cancer mutations, evaluation of new epigenetic markers to predict risk of recurrent disease in those with early stage lung cancer, studying the impact of LKB1 mutations in outcome for early stage lung cancer and testing novel methods to overcome resistance to targeted therapies. RELEVANCE: This proposal will study novel translational strategies to improve the outcomes for lung cancer. This center will focus on biomarker discovery; novel methods to detect dominant oncogenic mutations using peripheral blood, new strategies to overcome resistance to targeted therapies and will attempt to validate the findings in ongoing and planned ECOG-ACRIN clinical trials.