ECOG-ACRIN Thoracic Malignancies Integrated Translational Science Center

描述（申请人提供）：随着新的分子靶点的发现和个体化治疗方案的发展，肺癌的治疗进入了一个新的时代。对于具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时间。然而，出现了对治疗的耐药性，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。为了实现这一目标，我们需要找到新的方法来监测患者对特定靶向治疗的耐药性。另一个研究领域涉及开发新的生物标志物，以识别有复发风险的患者或对特定治疗药物的敏感性。基因组学、表观遗传学和蛋白质组学领域的新发展使这些技术能够应用于国家临床试验网络（NCTN）最近和新的临床试验的患者标本。ECOG-ACRIN小组打算建立一个转化科学中心，主要关注胸部恶性肿瘤，以开发治疗肺癌的新方法，并开发新的生物标志物，随后可在前瞻性临床试验中进行测试。胸部恶性肿瘤综合转化科学中心的主要目标是：1。开发基因组学、表观基因组学和蛋白质组学方法，以加强正在进行和计划中的ECOG-ACRIN研究中的生物标志物发现工作；2. 对现有肺癌肿瘤标本进行试点研究，以开展基于生物标志物的前瞻性临床试验；和3。快速翻译ECOG-ACRIN胸科委会在临床试验中开展的试点项目和生物标志物发现工作的结果。在拟议的试点项目中，突出的项目包括利用血浆DNA标本识别目标癌症突变，评估新的表观遗传标记来预测早期肺癌患者疾病复发的风险，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的新方法。

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.