Emory University Lung Cancer SPORE

概述摘要/摘要 肺癌是与癌症相关的死亡的主要原因，全球每年有160多万人死亡。它是 通常在晚期确诊，并与大多数患者的不良结局有关。这 埃默里大学肺癌孢子奖的申请汇集了一位杰出的和多方面的 由肿瘤学家、免疫学家、药物发现专家和翻译研究人员组成的学科团队致力于 致力于肺癌研究，以解决关键问题，从而改善这种致命疾病患者的预后 疾病。我们提议的计划将在肺癌管理的两个关键领域产生重大影响： 通过发展免疫治疗提高免疫治疗的疗效和克服治疗耐药性 新型分子靶向制剂。通过这个高度协作的 敬业的研究人员，并基于我们的团队自 上一次的孢子申请，今次修订后的申请旨在大幅改善 通过三个总体具体目标管理非小细胞肺癌(NSCLC)患者：目标1： 评估干细胞样T细胞并提高检查点抑制剂在非小细胞肺癌中的疗效(项目1)；目标2： 以MERTK为靶点以改善EGFR突变的NSCLC的预后(项目2)；目标3：以Bax为靶点 非小细胞肺癌中克服治疗耐药性的信号(项目3)。埃默里肺癌孢子计划 将通过与行政核心(核心1)、病理核心(核心2)和 生物统计和生物医学信息学核心(核心3)，并将进行职业提升和 发展研究计划(CEP和DRP)。孢子计划将受益于定期的建议和 外部和内部咨询委员会成员就其进展和方向提出的建议。我们的 该计划将得到强有力的制度支持，包括现代化的研究空间，优秀的共享资源， 以及来自埃默里大学温希普癌症研究所的大量配套资金(总计225万美元) (NCI指定的综合癌症中心)，埃默里大学伍德拉夫健康科学中心，埃默里 医疗保健系统，埃默里医学院，以及血液病和内科肿瘤科。 通过团队推动的免疫疗法和分子靶向疗法的创新研究，我们 有信心这个孢子计划，与其他肺癌孢子站点合作，将有一个主要的 对肺癌的管理产生积极影响。

OVERVIEW SUMMARY/ABSTRACT Lung cancer is the leading cause of cancer-related deaths, with more than 1.6 million deaths/year globally. It is often diagnosed at an advanced stage and is associated with poor outcomes for the majority of patients. This application for a lung cancer SPORE award from Emory University brings together an outstanding and multi- disciplinary team of oncologists, immunologists, drug discovery experts, and translational researchers dedicated to lung cancer research to address critical questions that will improve the outcome for patients with this lethal disease. Our proposed program will have significant impact in two crucial areas of lung cancer management: enhancing the efficacy of immunotherapy and overcoming treatment resistance through the development of novel molecularly targeted agents. Through strong teamwork carried out by this highly collaborative team of dedicated investigators, and building on exciting data published in leading journals by our group since our previous SPORE application, this revised submission aims to achieve substantial improvements in the management of patients with non-small cell lung cancer (NSCLC), through three overall Specific Aims: Aim 1: To evaluate stem-like T cells and improve efficacy of checkpoint inhibitors in NSCLC (Project 1); Aim 2: To target MERTK to improve outcomes for EGFR-mutated NSCLC (Project 2); and Aim 3: To target Bax signaling to overcome treatment resistance in NSCLC (Project 3). The Emory Lung Cancer SPORE program will be supported by close interaction with the Administrative Core (Core 1), Pathology Core (Core 2) and the Biostatistics and Biomedical Informatics Core (Core 3), and will conduct Career Enhancement and Developmental Research Programs (CEP and DRP). The SPORE program will benefit from regular advice and recommendations from External and Internal Advisory Board members regarding its progress and direction. Our program will receive strong institutional support including modern research space, excellent shared resources, and a significant level of matching funds (totaling $2.25M) from the Winship Cancer Institute of Emory University (an NCI-designated Comprehensive Cancer Center), Emory University Woodruff Health Sciences Center, Emory Healthcare System, Emory School of Medicine, and the Department of Hematology and Medical Oncology. Through team-driven innovative research efforts in immunotherapies and molecularly targeted therapeutics, we are confident that this SPORE program, in collaboration with other lung cancer SPORE sites, will have a major positive impact on the management of lung cancer.