Yale SPORE in Lung Cancer (YSILC): The Biology and Personalized Treatment of Lung Cancer

耶鲁大学肺癌分生孢子(YSILC)总体总结 原发癌和转移性肺癌的生物学和个体化治疗：YSILC联合 横跨癌症研究不同领域的翻译科学家齐聚一堂，共同应对 肺癌。YSILC的目标是通过开发新的 治疗方法和治疗方法是基于对靶向生化和 参与肺癌进展、耐药性获得和发展的免疫学途径 转移YSILC翻译研究团队将通过三个项目实现这一目标： 项目1：测试Siglec-15(S15)是PD-L1/B7-H1阴性患者的主要免疫抑制因子的假设 肺癌和阻断S15对部分肺癌患者有效；项目2： 评价对抗EGFR突变肺中酪氨酸激酶抑制剂耐药性的机制方法 癌症；项目3：针对肺癌转移和中枢神经系统的耐药性。那里 有三个核心(行政；生物统计和生物信息学；以及生物谱学、病理学和基因组学) 支持项目及其临床目标、机制研究和临床生物标记物的评估 申请。强大的发展研究和职业提升计划(DRP、CEP)，具有 还提出了选择各种和富有成效的项目并取得良好结果的历史。高度的 协调的YSILC项目、核心和计划专注于开发新的肺癌疗法， 病人样本的分析、基于细胞的分析、人类细胞系的生产和疾病的动物模型 作为设计前瞻性试验的指南，将这些创新的有针对性的方法转化为临床治疗。 这些项目中的每一个都有一个临床试验(要么是由研究者发起的，要么是基于NCI的)，旨在测试 新疗法的敏感性和耐药性与分子相关。预期的翻译结果 该计划包括：(1)发现一种高度协调和集中开发的新型免疫制剂 在我们目前的孢子研究中；(2)对沙门氏菌的遗传和表观遗传机制有了更好的理解 对EGFR治疗的抵抗力及其克服方法；(3)对大脑潜在机制的理解 (4)通过发展下一代肺癌研究，扩大肺癌研究的广度 研究人员和鼓励其他领域的老牌研究人员继续进行肺癌研究 通过我们的CEP和DRP计划。

YALE SPORE IN LUNG CANCER (YSILC) OVERALL SUMMARY The Biology and Personalized Treatment of Primary and Metastatic Lung Cancer: The YSILC unites translational scientists spanning diverse areas of cancer research to converge on addressing the challenge of lung cancer. The goal of the YSILC is to reduce mortality from lung cancer through development of novel therapeutics and treatment approaches that are based on an understanding of targetable biochemical and immunological pathways involved in progression of lung cancer, acquisition of resistance, and development of metastasis The YSILC translational research team will accomplish this objective through three projects: Project 1: Test the hypotheses that Siglec-15 (S15) is a major immune suppressor in PD-L1/B7-H1-negative lung cancer and that blockade of S15 can be efficacious for a subset of lung cancer patients; Project 2: Evaluate mechanism-based approaches to counter tyrosine kinase inhibitor resistance in EGFR-mutant lung cancer; Project 3: Targeting lung cancer metastasis and drug resistance in the central nervous system. There are three Cores (Administrative; Biostatistics and Bioinformatics; and Biospecimen, Pathology, and Genomics) to support the projects and their clinical aims, mechanistic studies, and evaluation of biomarkers for clinical application. Strong Developmental Research and Career Enhancement Programs (DRP, CEP) with a history of choosing diverse and productive projects with good outcomes are also proposed. The highly coordinated YSILC projects, cores, and programs are focused on developing novel lung cancer therapies, with analysis of patient samples, cell-based assays, production of human cell lines and animal models of disease as a guide to design prospective trials that translate these innovative targeted approaches to clinical therapies. Each of these projects has a clinical trial (either investigator-initiated or NCI-based) designed to test the sensitivity and resistance of the new therapy with molecular correlates. The expected translational outcomes of the program include: (1) a highly coordinated and focused development of a novel immune agent discovered during our current SPORE research; (2) an improved understanding of genetic and epigenetic mechanisms of resistance to EGFR therapies and how to combat it; (3) an understanding of the mechanism underlying brain metastasis; (4) expanding the breadth of lung cancer research by developing the next generation of investigators and encouraging established investigators in other fields to pursue studies on lung cancer through our CEP and DRP programs.